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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Distribution of HIV-1 plasma viral loads &#40;log10&#41; by the genotypes of the <span class="elsevierStyleItalic">ccr5</span> &#40;a&#41;&#44; <span class="elsevierStyleItalic">IL-6</span> &#40;b&#41;&#44; <span class="elsevierStyleItalic">IL-10</span> &#40;c&#41;&#44; and <span class="elsevierStyleItalic">IFN-&#947;</span> &#40;d&#41; genes in the HIV-1 seropositive group&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Susceptibility to Human Immunodeficiency Virus &#40;HIV-1&#41; infection and the rate of disease progression to acquired immunodeficiency syndrome &#40;AIDS&#41; varies widely among the individuals&#44; in part related to host genetic factors such as human leukocyte antigen &#40;HLA&#41; B and C molecules and chemokine receptors and their ligands&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> Genetic cohort studies have shown association of several single nucleotide polymorphisms &#40;SNP&#41; with different rates of progression and variation in susceptibility to infection&#46; These SNPs have been reported in genes encoding molecules that participate in the attachment process and viral penetration into the host cell &#40;CCR5&#44; CCR2&#44; RANTES&#44; and SDF1&#41;&#44; in the regulation of the immune response &#40;IL-10&#44; TNF&#945;&#44; and MBL&#41;&#44; and in the recognition of epitopes of viral antigens by CD4&#43; and CD8&#43; T lymphocytes &#40;HLA class I and II molecules&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The chemokine receptor CCR5 acts as a coreceptor for the HIV-1 entry with the CD4 molecule as the main receptor expressed on CD4&#43; T cells&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Both receptors interact with the gp120 molecule on the HIV virion surface&#46; The Genome-Wide Association Study &#40;GWAS&#41; dataset revealed that loss of CCR5 function in the CCR5-&#916;32 homozygous genotype&#44; due to a 32-bp deletion&#44; confers resistance to HIV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> More complexity in <span class="elsevierStyleItalic">CCR5</span> genomic regulation is introduced by numerous SNPs and epigenetic variants&#44; which have been found to be associated with the susceptibility to HIV infection and the outcome of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Interleukin &#40;IL&#41;-6 is one of several pro-inflammatory cytokines involved in the systemic and chronic immune response&#46; Higher circulating levels of this cytokine have been reported in non-surviving rather than surviving septic patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;10</span></a> In addition&#44; an association between IL-6 promoter polymorphism &#40;&#8722;174&#8239;G&#47;C&#41; and circulating levels of the molecule has been found in different diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> The influence of IL-6 promoter polymorphism &#40;&#8722;174&#8239;G&#47;C&#41; on sepsis risk and sepsis-related mortality has been addressed in other studies&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In fact&#44; different IL-6 levels at different stages of HIV infection have been identified as it is secreted to activate the immune response against the virus and eliminate the primary HIV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A SNP at position &#8722;1082 of the proximal promoter region of the IL-10 gene &#40;rs1800896&#41; has been associated with differential levels of IL-10 production across three genotypes &#40;&#8722;1082&#8239;GG&#44; &#8722;1082&#8239;GA&#44; and &#8722;1082&#8239;AA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In the same way&#44; the &#8722;1082&#8239;AA genotype has also been associated with a higher probability of HIV type 1 &#40;HIV-1&#41; acquisition&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Several polymorphisms in the promoter region of the IFN-&#947; gene&#44; in particular those at position &#43;874&#44; are considered to influence the levels of expression of this cytokine&#46; Thus&#44; some studies have demonstrated the association of this SNP with susceptibility towards or severity of AIDS&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The genetic variants of cytokines&#44; which modulate the infection and replication of HIV&#8208;1&#44; can potentially influence disease progression and the ability of HIV&#8208;1 to alter the delicate balance in apoptosis-related gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Immunogenic cytokine profiles &#40;TNF<span class="elsevierStyleItalic">&#945;</span>&#44; IFN-<span class="elsevierStyleItalic">&#947;</span>&#44; TGF<span class="elsevierStyleItalic">&#946;</span>&#44; IL-10&#44; and IL-6&#41; have been widely described as important factors associated with susceptibility and evolution of HIV-1 infection&#44; but few works have focused on patients of the HIV&#47;AIDS Cuban population&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> An allelic frequency of 7&#37;&#8211;8&#37; for the CCR5&#916;32 has been reported in the general population of Cuba&#44; similar to 13&#37; reported in elderly Cuban patients infected with HIV-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The present study aimed to estimate the frequency of CCR5&#916;32&#44; IL-6-174G&#47;C&#44; IFN-<span class="elsevierStyleItalic">&#947;</span>&#43;874T&#47;A and IL-10-1082A&#47;G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on susceptibility to and disease progression in real life situations&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Population and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Population</span><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 120 subjects registered at the Institute of Tropical Medicine &#8220;Pedro Kour&#236;&#8221; &#40;IPK&#41; and Hospital Cl&#237;nico Quir&#250;rgico &#8220;Hermanos Ameijeiras&#8221; &#40;HHA&#41;&#44; were included from June 2018 until December 2019&#46; The subjects were divided into two groups&#44; group 1&#58; 61 HIV-1 positive individuals under antiretroviral therapy &#40;ART&#41; and group 2&#58; 59 exposed HIV-1 seronegative individuals &#40;tested for HIV at inclusion&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The participants that were eligible for this study were individuals who had ever been in an ongoing heterosexual and homosexual relationship for at least 6 months and were 18 years of age or older&#46; The intention of the research was to include a diverse profile of participants including those who had ever experienced having an HIV test either alone or with their sexual partner&#47;s&#46; Group 2 &#40;exposed uninfected subjects&#41; were individuals who visit the same clinic as their sexual partner&#47;s and exposed to HIV infection&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">This study was approved by the research ethics committee of IPK &#40;CEI-IPK 63-18&#41; and HHA &#40;CEI-HHA 27-18&#41;&#44; respectively&#46; All individuals who agreed to participate in the study signed an informed consent form&#46; Demographic characteristics of individuals were collected&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0055" class="elsevierStylePara elsevierViewall">Plasma HIV-1 viral loads were determined using the Nuclisens Easy Q HIV-1 kit v2&#46;0 &#40;Biom&#233;rieux&#44; France&#41;&#44; which has a minimum detection limit of 10 RNA copies&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> CD4&#43; cell counts were performed by flow cytometer &#40;CyFlow Space PARTEC&#44; Germany&#41; using a CD4&#43; count kit &#40;Partec&#44; Germany&#41; according to the standard protocol recommended by the manufacturer&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">To Polymorphisms Identification&#44; DNA was extracted from peripheral blood mononuclear cells using the commercial kit Qiagen DNeasy&#174; Blood &#38; Tissue &#40;Hilden&#44; Germany&#41;&#46; Amplification of fragments of the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes was performed by Polymerase Chain Reaction &#40;PCR&#41; followed by identification of polymorphisms using the Restriction Fragment Length Polymorphism analysis &#40;RFLP&#41; for IL-6 with the restriction enzymes Nla III &#40;Sigma&#44; USA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Amplification Refractory Mutation System &#40;ARMS-PCR&#41; was used for IFN-<span class="elsevierStyleItalic">&#947;</span>&#44; and IL-10 genes&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Subsequently&#44; the amplified products were subjected to electrophoresis in 4&#37; agarose gels containing 2&#46;5&#8239;&#181;L of ethidium bromide gel stain &#40;10&#8239;mg&#47;mL&#41; &#40;Sigma&#44; USA&#41;&#46; The alleles and expected fragments of each amplified gene are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The distributions of allele and genotype frequencies for each polymorphism in the groups were estimated by direct counting and compared using the chi-square test or Fisher&#8217;s exact test in cases when 2 or more 2 polymorphism features were compared&#46; The testing for Hardy&#8211;Weinberg equilibrium was evaluated using the chi-square test&#46; The comparison among genotypes versus the wild-type allele considering HIV progression markers &#40;CD4&#43; cells and viral load&#41; was evaluated using the Mann&#8211;Whitney test&#46; The combination of SNP analysis &#40;when more than one SNP is included&#41; was performed by SNPSstats &#40;<a href="http://bioinfo.iconcologia.net/SNPSstats">http&#58;&#47;&#47;bioinfo&#46;iconcologia&#46;net&#47;SNPSstats</a>&#41;&#46; A 5&#37; significance level &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#8804;&#8239;0&#46;05&#41; was considered in all statistical analyses using the software Epidat version 3&#46;1 and GraphPad Prism 9&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">The demographic characteristics of the groups under study are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Most of the included patients were in the range from 20 to 29 years of age in both groups&#44; which account for 28&#37; and 54&#37; of each cohort&#44; respectively&#46; The predominant skin color was white with 59&#37; in both groups&#46; Heterosexual orientation was predominant in both groups with 61&#37; and 93&#37;&#44; respectively&#59; it is important to note that they were statistically different &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46; In this regard&#44; 31&#37; of men who have sex with men behaved in the group of seropositive patients versus 7&#37; in the group of exposed non-infected patients&#44; which may explain the previous difference&#46; As for gender&#44; also a significant difference was observed with 72&#37; of men in the group of seropositive patients and 80&#37; of women in the group of HIV-1-exposed seronegative persons &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">An analysis of deviations between the observed and expected allele and genotype proportions in both groups revealed that both groups were in Hardy&#8211;Weinberg equilibrium &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; for <span class="elsevierStyleItalic">ccr5</span> and <span class="elsevierStyleItalic">IL-6</span> polymorphisms&#46; However&#44; in the case of <span class="elsevierStyleItalic">IL-10</span>&#44; both groups were in Hardy&#8211;Weinberg imbalance &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46; In addition&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> was in Hardy&#8211;Weinberg imbalance &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41; in the group of seropositive HIV-1 patients&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; it is shown that the allelic and genotypic distributions of the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span>&#44; and <span class="elsevierStyleItalic">IL-10</span> genes did not differ significantly &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; between the two groups&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">To assess the impact of gene polymorphisms on AIDS progression&#44; CD4 absolute counts were considered&#46; The cell counts values did not differ significantly &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; among the genotypes of the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes&#46; Next&#44; we performed a similar assessment considering the viral load&#46; Distribution of genotype frequencies by plasma viral load values did not differ significantly &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; among the genotypes of the <span class="elsevierStyleItalic">ccr5&#44; IL-10</span>&#44; and <span class="elsevierStyleItalic">IFN-&#947;</span>&#46; On the contrary&#44; it was observed significant differences &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41; among genotypes of the <span class="elsevierStyleItalic">IL-6</span> gene&#44; and the IL-6 GC genotype was associated with higher viral load values &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The combination of SNP analysis is shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; Of the 16 possible combinations of different alleles&#44; nine were identified in this study&#46; In fact&#44; 2 combinations of SNP &#40;1 and 2&#41; accumulate a frequency of 59&#46;25&#37;&#46; One combination of SNP &#40;9&#41; showed a highly significant increased risk of HIV infection but with very low frequency &#40;&#60;1&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The genetic factors that contribute to susceptibility or progression of HIV&#47;AIDS probably involve an interaction between multiple gene alleles located on different chromosomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;13</span></a> Consequently&#44; rather than merely performing a polymorphism association study for a single gene&#44; we chose to investigate the functional significance of the relationship between four single nucleotide polymorphisms located in the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes and diseases progression in a cohort of Cuban HIV&#47;AIDS patients&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In this investigation&#44; for both groups&#44; most of the subjects ranged from 20 to 29 years&#44; like what Cobas-Planchez et al&#46; reported in 2022 for HIV-patients in the municipality of Havana&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In the group of HIV patients&#44; the male sex was predominant as reported in Cuba since the beginning of the pandemic&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Although in the Cuban epidemic&#44; most of the seropositive men who have sex with men &#40;HSH&#41;&#44; in our study most of the subjects were heterosexual according to their opinion collected in the survey&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">We have found that ccr5 and IL-6 polymorphism were in Hardy&#8211;Weinberg equilibrium&#46; It was not the case for <span class="elsevierStyleItalic">IL-10</span> and <span class="elsevierStyleItalic">IFN-&#947;</span>&#46; This result might suggest the selection of the <span class="elsevierStyleItalic">IL10</span> allele in the population or it can be indicative that the polymorphism can be associated with the illness&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The study HapMap gene expression showed that genes with the greatest with-in-population expression variability are significantly enriched for chemokine signaling associated with HIV-1 infection&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> This information is very important for future studies that involve cytokines genes and HIV infection&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The frequency of the ccr5&#916;32 is quite variable&#46; In general&#44; the &#916;32 allele frequency is high in European-derived populations &#40;for example&#44; 16 &#37; in Norway and 11&#37; in Germany&#41; and low or absent in African and Asian populations&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;23</span></a> However&#44; although the &#916;32 allele is more frequent in European populations&#44; there are exceptions due to migratory events&#46; For example&#44; the frequency of the &#916;32 allele is high in South Africa &#40;13&#37;&#41; and Chile &#40;12&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In Brazil&#44; the frequency of the allele in the general population is around 4&#37;&#8211;5&#37;&#46; In Cuba&#44; the frequency of the allele in the general population is around 7&#37;&#8211;8&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;24</span></a> We found the frequency of the allele in the exposed HIV-1&#44; in the not infected group was around 7&#37; and&#44; in the HIV-group was around 10&#37;&#44; without statistically significant differences&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Some studies have indicated a significantly higher risk of infection and progression to AIDS of the homozygous IFN-<span class="elsevierStyleItalic">&#947;</span>-874A&#47;T polymorphism in patients infected with HIV-1&#44; like the result found in this study&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;25</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The effects and mechanisms of IL-10 action in the pathogenesis of HIV-1 are quite controversial&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;19</span></a> In our study&#44; the IL-10 SNP-1082 GA genotype was found at the highest frequency&#44; followed by &#8722;1082&#8239;AA and GA&#46; A similar pattern was found in two previous studies in which no associations of any of the IL-10 SNPs with CD4&#43; cell counts&#44; or viral load were found&#44; as well as in our study&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a> In the same line&#44; Naicker et al&#46; reported that there was no significant difference in the distribution of IL-10 genotypes at position &#8722;1082 between the HIV-negative and HIV-positive groups like in the present study&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The SNP polymorphism was analyzed for its association with the most common biomarker of disease progression&#44; CD4&#43; cell levels and viral load and we found that CD4&#43; cells count values did not differ significantly between the studied genotypes&#44; as already published&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> But it differs from what was found by Al-Jabri et al in a study of <span class="elsevierStyleItalic">ccr5</span> nucleotide variants and haplotypes that showed that the common HHC haplotype was significantly associated with a higher average of CD4&#43; T-cell counts among the Omani HIV-1-infected patients &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;024&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Joshi et al&#46; in 2017 demonstrated that ccr5 promoter polymorphisms correlate with CD4 T cell loss maybe by regulating CD4 T cell apoptosis in HIV patients&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">We found some association between the IL-6 GC polymorphism with values of high viral load above 5000 RNA copies&#47;&#181;L&#46; Previously&#44; Borges et al&#46; found that HIV replication was associated with significantly increased IL-6 levels&#46; There was apparently a dose-response effect with increasing fold differences in IL-6 secretion with higher HIV RNA plasma levels&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In another study&#44; Sherman et al&#46; found forty variants associated with IL-6 levels in the transethnic group&#46; These authors identified that the increased level of IL-6 could be the result of increased levels of sIL-6R &#40;variant rs4133213 related to plasma&#41; as the binding of IL-6 by sIL-6R could protect IL-6 from degradation&#46; When IL-6 binds to sIL-6R&#44; it can trigger the trans-signaling pathway&#44; which is responsible for the pro-inflammatory action of IL-6&#46; These findings support the notion that host genetics contribute to chronic inflammation in HIV individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Also&#44; variability in viral load is influenced by host&#44; viral&#44; and environmental factors&#44; including human genetic variation&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The mechanisms of altered gene expression associated with polymorphisms are still poorly understood&#46; There is evidence that sequence changes in the noncoding regions of cytokine genes may influence the production of the corresponding products&#44; due to linkage with another marker directly affecting gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">When the objective of a study is to identify whether several polymorphisms or variants of genes are related to a disease or not&#44; it must be determined if the genes are in linkage disequilibrium &#40;LD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> This analysis is fundamental to the investigation on genetic architecture of complex traits in human disease&#44; and population structure and evolution dynamics&#46; However&#44; until now&#44; studies primarily focus on LD status between genetic variants located on the same chromosome&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> In this study&#44; the four evaluated genes were located on different chromosomes &#40;e&#46;g&#46;&#44; <span class="elsevierStyleItalic">ccr5</span> &#40;3p21&#46;31&#41;&#44; <span class="elsevierStyleItalic">IL-6</span> &#40;7p15&#46;3&#41;&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> &#40;12q&#46;15&#41; and <span class="elsevierStyleItalic">IL-10</span> &#40;1q32&#46;1&#41;&#41; therefore they segregate independently&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">AIDS is a consequence of the interaction between the individual&#8217;s genetic background and the environmental factors faced by the individual&#44; in which gene-gene interaction may play a significant role&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In this study&#44; only one combination of SNPs shows a highly significant increased risk of HIV infection but with very low frequency &#40;&#60;1&#37;&#41;&#46; However&#44; we cannot conclude that it is really responsible for modifying the risk of the disease&#46; For this&#44; it would be necessary to have information from functional studies that demonstrated a different biological effect compared to the most frequent combination&#46; Further experiments should address this point in the future&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">This study has some limitations&#58; i&#41; the size sample &#40;two groups with 120 patients&#41;&#44; ii&#41; the retrospective and transversal study&#44; iii&#41; the limited number of cytokines polymorphisms evaluated in connection with the HIV-1 infection and iv&#41; the seropositive persons included in the study were under treatment and this could impact on disease progression&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In any case&#44; this study has value in that it is the first&#44; to our knowledge&#44; in reporting genetic profiles of coreceptors and cytokines in patients infected with HIV-1 and patients exposed and not infected&#44; and their influence on susceptibility and disease progression in real life situations in Cuba&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This research received no external funding&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of Interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Institutional review board statement</span><p id="par0170" class="elsevierStylePara elsevierViewall">The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of IPK and HHA for studies involving humans&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Informed consent statement</span><p id="par0175" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all subjects involved in the study&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Genetic studies have shown associations of several single nucleotide polymorphisms &#40;SNP&#41; with different rates of progression and variation in susceptibility to HIV infection&#46; This study aimed to estimate the frequency of ccr5&#916;32&#44; IL-6-174G&#47;C&#44; IFN-&#947;&#43;874T&#47;A and IL-10-1082A&#47;G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine &#171;Pedro Kour&#187; &#40;IPK&#41; and the Ameijeiras Hospital from June 2018 until December 2019&#46; The amplification of fragments of the <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III&#46; Amplification Refractory Mutation System was used for <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The allelic and genotypic distributions of the genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> did not differ significantly between the two groups&#46; Cell counts and plasma viral load values did not differ significantly between genotypes of the <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes&#46; Only the IL-6 GC genotype was associated with higher viral load values&#46; The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them&#44; but with a very low frequency &#40;&#60;1&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduccion</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Los estudios gen&#233;ticos han demostrado asociaciones de varios polimorfismos de un solo nucle&#243;tido &#40;SNP&#41; con diferentes tasas de progresi&#243;n y variaci&#243;n en la susceptibilidad a la infecci&#243;n por VIH&#46; Este estudio tuvo como objetivo estimar la frecuencia de los polimorfismos ccr5&#916;32&#44; IL-6-174G&#47;C&#44; IFN-&#947;&#43;874T&#47;A e IL-10-1082A&#47;G en pacientes cubanos infectados por VIH y un grupo de parejas serodiscordantes para evaluar su influencia sobre el riesgo y la progresi&#243;n de la enfermedad&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio transversal en 120 sujetos atendidos en el Instituto de Medicina Tropical &#171;Pedro Kour&#187; &#40;IPK&#41; y el Hospital Hermanos Ameijeiras entre junio de 2018 y diciembre de 2019&#46; La amplificaci&#243;n de los fragmentos de los genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span> se realiz&#243; mediante reacci&#243;n en cadena de la polimerasa seguida por el an&#225;lisis del polimorfismo de fragmentos de restricci&#243;n utilizando la enzima Nla III para la IL-6&#46; El Sistema de Mutaci&#243;n Refractario a la Amplificaci&#243;n por PCR se utiliz&#243; en el caso de los genes <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span>&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Las distribuciones al&#233;licas y genot&#237;picas de los genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span> no difirieron significativamente entre los dos grupos&#46; Los recuentos celulares y los valores de carga viral en plasma no difirieron significativamente entre los genotipos de los genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span>&#46; S&#243;lo el genotipo IL-6 GC se asoci&#243; con valores m&#225;s altos de carga viral&#46; La combinaci&#243;n de alelos de los cuatro SNP considerados mostr&#243; un aumento muy significativo del riesgo de infecci&#243;n por VIH para uno de ellos&#44; pero con una frecuencia muy baja &#40;&#60; 1&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Este estudio contribuye a evaluar la frecuencia de estos polimorfismos y su influencia en los biomarcadores de la progresi&#243;n de la infecci&#243;n por VIH en la poblaci&#243;n cubana con infecci&#243;n por el VIH&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Distribution of HIV-1 plasma viral loads &#40;log10&#41; by the genotypes of the <span class="elsevierStyleItalic">ccr5</span> &#40;a&#41;&#44; <span class="elsevierStyleItalic">IL-6</span> &#40;b&#41;&#44; <span class="elsevierStyleItalic">IL-10</span> &#40;c&#41;&#44; and <span class="elsevierStyleItalic">IFN-&#947;</span> &#40;d&#41; genes in the HIV-1 seropositive group&#46;</p>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-GCTCTCTCCCAGGAATCATC-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#176;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deletion &#916;32 pb</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-CGAGAGAGGGTCCTTAGTAG-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-6</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;174&#8239;G&#47;C &#40;promoter&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-6F</span>&#58; 5&#697;-AAGGAAGAGTGGTTCTGCTTCT-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#176;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;Nla III&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&#58; 85&#44; 84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-6R</span>&#58; 5&#697;-ATCTTTGTTGGAGGGTGAGG-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&#58; 169&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-10</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;1082&#8239;G&#47;A &#40;promoter&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primer generic antisense&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#176;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&#58; 550&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-CAGCCCTTCCATTTTACTTTC-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&#58; 550</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-10G</span>&#58; 5&#697;-TACTAAGGCTTCTTTGGGAG-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-10A</span>&#58; 5&#697;-CTACTAAGGCTTCTTTGGGAA-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IFN-&#947;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;874&#8239;T&#47;A &#40;promoter&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primer generic antisense&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#176;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&#58; 261&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-TCAACAAAGCTGATACTCCA-3&#697;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T&#58; 261</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IFN-&#947; A</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-TTCTTACAACACAAAATCAAATCA-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IFN-&#947; T</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-TTCTTACAACACAAAATCAAATCT-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients n&#8239;&#61;&#8239;61</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients n&#8239;&#61;&#8239;59</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of persons&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of persons&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>20&#8211;29 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9999</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>30&#8211;39 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>40&#8211;49 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>50&#8211;59 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  """
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                  \t\t\t\t" scope="col">Genotypes and alleles&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;6667 &#40;0&#46;1782&#8211;2&#46;494&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7434</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ccr5</span> wt&#47;&#916; 32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Wt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;6784 &#40;0&#46;1864&#8211;2&#46;468&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7490</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#916;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genotype <span class="elsevierStyleItalic">IL-6</span> G&#47;G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;4700 &#40;0&#46;6661&#8211;3&#46;2440&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;2213</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype G&#47;C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype C&#47;C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8259 &#40;0&#46;4113&#8211;1&#46;658&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;6012</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genotype <span class="elsevierStyleItalic">IL-10</span> A&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5000 &#40;0&#46;3131&#8211;7&#46;1856&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7631</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype G&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype G&#47;G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;065 &#40;0&#46;6409&#8211;1&#46;768&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8971</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genotype <span class="elsevierStyleItalic">IFN-&#947;</span> A&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0000 &#40;0&#46;5825&#8211;6&#46;8667&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5136</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype T&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype T&#47;T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;259 &#40;0&#46;75786&#8211;2&#46;093&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4379</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3457837.png"
              ]
            ]
          ]
        ]
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Original article
Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients
Polimorfismos de los genes CCR5, IL-6, IFN-γ e IL-10 en pacientes cubanos con VIH/sida
D. Hernández Requejoa,1, Y. de Armasb,c,1, E. Iglesiasd, H.M. Díaze, R. Gravierf, M.C. Godínez Lópeza, L. Fonteg, M. Plascencia-Cruzh, K. Pacheco-Quijanoh, J. Palomaresh, H.R. Pérez-Gómezh, A. Plascencia-Hernándezh,
Corresponding author
aplascenciah@yahoo.com.mx

Corresponding authors.
, E.J. Calderóni,j,k,
Corresponding author
ecalderon@us.es

Corresponding authors.
a Departamento de Laboratorio Clínico, Centro Hospitalario, Instituto de Medicina Tropical «Pedro Kourí», La Habana, Cuba
b Departamento de Patología, Centro Hospitalario, Instituto de Medicina Tropical «Pedro Kourí», La Habana, Cuba
c Departamento de Diagnóstico Microbiológico Clínico, Centro Hospitalario, Instituto de Medicina Tropical «Pedro Kourí», La Habana, Cuba
d Centro de Ingeniería Genética y Biotecnología, La Habana, Cuba
e Hospital Clínico Quirúrgico «Hermanos Ameijeiras», La Habana, Cuba
f Departamento de Farmacología, Instituto de Medicina Tropical «Pedro Kourí», La Habana, Cuba
g Departamento de Parasitología, Instituto de Medicina Tropical «Pedro Kourí», La Habana, Cuba
h Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
i Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain
j Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
k Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Distribution of HIV-1 plasma viral loads &#40;log10&#41; by the genotypes of the <span class="elsevierStyleItalic">ccr5</span> &#40;a&#41;&#44; <span class="elsevierStyleItalic">IL-6</span> &#40;b&#41;&#44; <span class="elsevierStyleItalic">IL-10</span> &#40;c&#41;&#44; and <span class="elsevierStyleItalic">IFN-&#947;</span> &#40;d&#41; genes in the HIV-1 seropositive group&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Susceptibility to Human Immunodeficiency Virus &#40;HIV-1&#41; infection and the rate of disease progression to acquired immunodeficiency syndrome &#40;AIDS&#41; varies widely among the individuals&#44; in part related to host genetic factors such as human leukocyte antigen &#40;HLA&#41; B and C molecules and chemokine receptors and their ligands&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a> Genetic cohort studies have shown association of several single nucleotide polymorphisms &#40;SNP&#41; with different rates of progression and variation in susceptibility to infection&#46; These SNPs have been reported in genes encoding molecules that participate in the attachment process and viral penetration into the host cell &#40;CCR5&#44; CCR2&#44; RANTES&#44; and SDF1&#41;&#44; in the regulation of the immune response &#40;IL-10&#44; TNF&#945;&#44; and MBL&#41;&#44; and in the recognition of epitopes of viral antigens by CD4&#43; and CD8&#43; T lymphocytes &#40;HLA class I and II molecules&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The chemokine receptor CCR5 acts as a coreceptor for the HIV-1 entry with the CD4 molecule as the main receptor expressed on CD4&#43; T cells&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Both receptors interact with the gp120 molecule on the HIV virion surface&#46; The Genome-Wide Association Study &#40;GWAS&#41; dataset revealed that loss of CCR5 function in the CCR5-&#916;32 homozygous genotype&#44; due to a 32-bp deletion&#44; confers resistance to HIV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> More complexity in <span class="elsevierStyleItalic">CCR5</span> genomic regulation is introduced by numerous SNPs and epigenetic variants&#44; which have been found to be associated with the susceptibility to HIV infection and the outcome of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Interleukin &#40;IL&#41;-6 is one of several pro-inflammatory cytokines involved in the systemic and chronic immune response&#46; Higher circulating levels of this cytokine have been reported in non-surviving rather than surviving septic patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;10</span></a> In addition&#44; an association between IL-6 promoter polymorphism &#40;&#8722;174&#8239;G&#47;C&#41; and circulating levels of the molecule has been found in different diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> The influence of IL-6 promoter polymorphism &#40;&#8722;174&#8239;G&#47;C&#41; on sepsis risk and sepsis-related mortality has been addressed in other studies&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In fact&#44; different IL-6 levels at different stages of HIV infection have been identified as it is secreted to activate the immune response against the virus and eliminate the primary HIV infection&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A SNP at position &#8722;1082 of the proximal promoter region of the IL-10 gene &#40;rs1800896&#41; has been associated with differential levels of IL-10 production across three genotypes &#40;&#8722;1082&#8239;GG&#44; &#8722;1082&#8239;GA&#44; and &#8722;1082&#8239;AA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In the same way&#44; the &#8722;1082&#8239;AA genotype has also been associated with a higher probability of HIV type 1 &#40;HIV-1&#41; acquisition&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Several polymorphisms in the promoter region of the IFN-&#947; gene&#44; in particular those at position &#43;874&#44; are considered to influence the levels of expression of this cytokine&#46; Thus&#44; some studies have demonstrated the association of this SNP with susceptibility towards or severity of AIDS&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The genetic variants of cytokines&#44; which modulate the infection and replication of HIV&#8208;1&#44; can potentially influence disease progression and the ability of HIV&#8208;1 to alter the delicate balance in apoptosis-related gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Immunogenic cytokine profiles &#40;TNF<span class="elsevierStyleItalic">&#945;</span>&#44; IFN-<span class="elsevierStyleItalic">&#947;</span>&#44; TGF<span class="elsevierStyleItalic">&#946;</span>&#44; IL-10&#44; and IL-6&#41; have been widely described as important factors associated with susceptibility and evolution of HIV-1 infection&#44; but few works have focused on patients of the HIV&#47;AIDS Cuban population&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> An allelic frequency of 7&#37;&#8211;8&#37; for the CCR5&#916;32 has been reported in the general population of Cuba&#44; similar to 13&#37; reported in elderly Cuban patients infected with HIV-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The present study aimed to estimate the frequency of CCR5&#916;32&#44; IL-6-174G&#47;C&#44; IFN-<span class="elsevierStyleItalic">&#947;</span>&#43;874T&#47;A and IL-10-1082A&#47;G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on susceptibility to and disease progression in real life situations&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Population and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Population</span><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 120 subjects registered at the Institute of Tropical Medicine &#8220;Pedro Kour&#236;&#8221; &#40;IPK&#41; and Hospital Cl&#237;nico Quir&#250;rgico &#8220;Hermanos Ameijeiras&#8221; &#40;HHA&#41;&#44; were included from June 2018 until December 2019&#46; The subjects were divided into two groups&#44; group 1&#58; 61 HIV-1 positive individuals under antiretroviral therapy &#40;ART&#41; and group 2&#58; 59 exposed HIV-1 seronegative individuals &#40;tested for HIV at inclusion&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The participants that were eligible for this study were individuals who had ever been in an ongoing heterosexual and homosexual relationship for at least 6 months and were 18 years of age or older&#46; The intention of the research was to include a diverse profile of participants including those who had ever experienced having an HIV test either alone or with their sexual partner&#47;s&#46; Group 2 &#40;exposed uninfected subjects&#41; were individuals who visit the same clinic as their sexual partner&#47;s and exposed to HIV infection&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">This study was approved by the research ethics committee of IPK &#40;CEI-IPK 63-18&#41; and HHA &#40;CEI-HHA 27-18&#41;&#44; respectively&#46; All individuals who agreed to participate in the study signed an informed consent form&#46; Demographic characteristics of individuals were collected&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0055" class="elsevierStylePara elsevierViewall">Plasma HIV-1 viral loads were determined using the Nuclisens Easy Q HIV-1 kit v2&#46;0 &#40;Biom&#233;rieux&#44; France&#41;&#44; which has a minimum detection limit of 10 RNA copies&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> CD4&#43; cell counts were performed by flow cytometer &#40;CyFlow Space PARTEC&#44; Germany&#41; using a CD4&#43; count kit &#40;Partec&#44; Germany&#41; according to the standard protocol recommended by the manufacturer&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">To Polymorphisms Identification&#44; DNA was extracted from peripheral blood mononuclear cells using the commercial kit Qiagen DNeasy&#174; Blood &#38; Tissue &#40;Hilden&#44; Germany&#41;&#46; Amplification of fragments of the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes was performed by Polymerase Chain Reaction &#40;PCR&#41; followed by identification of polymorphisms using the Restriction Fragment Length Polymorphism analysis &#40;RFLP&#41; for IL-6 with the restriction enzymes Nla III &#40;Sigma&#44; USA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Amplification Refractory Mutation System &#40;ARMS-PCR&#41; was used for IFN-<span class="elsevierStyleItalic">&#947;</span>&#44; and IL-10 genes&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Subsequently&#44; the amplified products were subjected to electrophoresis in 4&#37; agarose gels containing 2&#46;5&#8239;&#181;L of ethidium bromide gel stain &#40;10&#8239;mg&#47;mL&#41; &#40;Sigma&#44; USA&#41;&#46; The alleles and expected fragments of each amplified gene are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The distributions of allele and genotype frequencies for each polymorphism in the groups were estimated by direct counting and compared using the chi-square test or Fisher&#8217;s exact test in cases when 2 or more 2 polymorphism features were compared&#46; The testing for Hardy&#8211;Weinberg equilibrium was evaluated using the chi-square test&#46; The comparison among genotypes versus the wild-type allele considering HIV progression markers &#40;CD4&#43; cells and viral load&#41; was evaluated using the Mann&#8211;Whitney test&#46; The combination of SNP analysis &#40;when more than one SNP is included&#41; was performed by SNPSstats &#40;<a href="http://bioinfo.iconcologia.net/SNPSstats">http&#58;&#47;&#47;bioinfo&#46;iconcologia&#46;net&#47;SNPSstats</a>&#41;&#46; A 5&#37; significance level &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#8804;&#8239;0&#46;05&#41; was considered in all statistical analyses using the software Epidat version 3&#46;1 and GraphPad Prism 9&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">The demographic characteristics of the groups under study are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Most of the included patients were in the range from 20 to 29 years of age in both groups&#44; which account for 28&#37; and 54&#37; of each cohort&#44; respectively&#46; The predominant skin color was white with 59&#37; in both groups&#46; Heterosexual orientation was predominant in both groups with 61&#37; and 93&#37;&#44; respectively&#59; it is important to note that they were statistically different &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46; In this regard&#44; 31&#37; of men who have sex with men behaved in the group of seropositive patients versus 7&#37; in the group of exposed non-infected patients&#44; which may explain the previous difference&#46; As for gender&#44; also a significant difference was observed with 72&#37; of men in the group of seropositive patients and 80&#37; of women in the group of HIV-1-exposed seronegative persons &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">An analysis of deviations between the observed and expected allele and genotype proportions in both groups revealed that both groups were in Hardy&#8211;Weinberg equilibrium &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; for <span class="elsevierStyleItalic">ccr5</span> and <span class="elsevierStyleItalic">IL-6</span> polymorphisms&#46; However&#44; in the case of <span class="elsevierStyleItalic">IL-10</span>&#44; both groups were in Hardy&#8211;Weinberg imbalance &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46; In addition&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> was in Hardy&#8211;Weinberg imbalance &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41; in the group of seropositive HIV-1 patients&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; it is shown that the allelic and genotypic distributions of the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span>&#44; and <span class="elsevierStyleItalic">IL-10</span> genes did not differ significantly &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; between the two groups&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">To assess the impact of gene polymorphisms on AIDS progression&#44; CD4 absolute counts were considered&#46; The cell counts values did not differ significantly &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; among the genotypes of the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes&#46; Next&#44; we performed a similar assessment considering the viral load&#46; Distribution of genotype frequencies by plasma viral load values did not differ significantly &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#62;&#8239;0&#46;05&#41; among the genotypes of the <span class="elsevierStyleItalic">ccr5&#44; IL-10</span>&#44; and <span class="elsevierStyleItalic">IFN-&#947;</span>&#46; On the contrary&#44; it was observed significant differences &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#60;&#8239;0&#46;05&#41; among genotypes of the <span class="elsevierStyleItalic">IL-6</span> gene&#44; and the IL-6 GC genotype was associated with higher viral load values &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The combination of SNP analysis is shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; Of the 16 possible combinations of different alleles&#44; nine were identified in this study&#46; In fact&#44; 2 combinations of SNP &#40;1 and 2&#41; accumulate a frequency of 59&#46;25&#37;&#46; One combination of SNP &#40;9&#41; showed a highly significant increased risk of HIV infection but with very low frequency &#40;&#60;1&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The genetic factors that contribute to susceptibility or progression of HIV&#47;AIDS probably involve an interaction between multiple gene alleles located on different chromosomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;13</span></a> Consequently&#44; rather than merely performing a polymorphism association study for a single gene&#44; we chose to investigate the functional significance of the relationship between four single nucleotide polymorphisms located in the <span class="elsevierStyleItalic">ccr5&#44; IL-6&#44; IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes and diseases progression in a cohort of Cuban HIV&#47;AIDS patients&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In this investigation&#44; for both groups&#44; most of the subjects ranged from 20 to 29 years&#44; like what Cobas-Planchez et al&#46; reported in 2022 for HIV-patients in the municipality of Havana&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In the group of HIV patients&#44; the male sex was predominant as reported in Cuba since the beginning of the pandemic&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Although in the Cuban epidemic&#44; most of the seropositive men who have sex with men &#40;HSH&#41;&#44; in our study most of the subjects were heterosexual according to their opinion collected in the survey&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">We have found that ccr5 and IL-6 polymorphism were in Hardy&#8211;Weinberg equilibrium&#46; It was not the case for <span class="elsevierStyleItalic">IL-10</span> and <span class="elsevierStyleItalic">IFN-&#947;</span>&#46; This result might suggest the selection of the <span class="elsevierStyleItalic">IL10</span> allele in the population or it can be indicative that the polymorphism can be associated with the illness&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The study HapMap gene expression showed that genes with the greatest with-in-population expression variability are significantly enriched for chemokine signaling associated with HIV-1 infection&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> This information is very important for future studies that involve cytokines genes and HIV infection&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The frequency of the ccr5&#916;32 is quite variable&#46; In general&#44; the &#916;32 allele frequency is high in European-derived populations &#40;for example&#44; 16 &#37; in Norway and 11&#37; in Germany&#41; and low or absent in African and Asian populations&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;23</span></a> However&#44; although the &#916;32 allele is more frequent in European populations&#44; there are exceptions due to migratory events&#46; For example&#44; the frequency of the &#916;32 allele is high in South Africa &#40;13&#37;&#41; and Chile &#40;12&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In Brazil&#44; the frequency of the allele in the general population is around 4&#37;&#8211;5&#37;&#46; In Cuba&#44; the frequency of the allele in the general population is around 7&#37;&#8211;8&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;24</span></a> We found the frequency of the allele in the exposed HIV-1&#44; in the not infected group was around 7&#37; and&#44; in the HIV-group was around 10&#37;&#44; without statistically significant differences&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Some studies have indicated a significantly higher risk of infection and progression to AIDS of the homozygous IFN-<span class="elsevierStyleItalic">&#947;</span>-874A&#47;T polymorphism in patients infected with HIV-1&#44; like the result found in this study&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;25</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The effects and mechanisms of IL-10 action in the pathogenesis of HIV-1 are quite controversial&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;19</span></a> In our study&#44; the IL-10 SNP-1082 GA genotype was found at the highest frequency&#44; followed by &#8722;1082&#8239;AA and GA&#46; A similar pattern was found in two previous studies in which no associations of any of the IL-10 SNPs with CD4&#43; cell counts&#44; or viral load were found&#44; as well as in our study&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a> In the same line&#44; Naicker et al&#46; reported that there was no significant difference in the distribution of IL-10 genotypes at position &#8722;1082 between the HIV-negative and HIV-positive groups like in the present study&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The SNP polymorphism was analyzed for its association with the most common biomarker of disease progression&#44; CD4&#43; cell levels and viral load and we found that CD4&#43; cells count values did not differ significantly between the studied genotypes&#44; as already published&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> But it differs from what was found by Al-Jabri et al in a study of <span class="elsevierStyleItalic">ccr5</span> nucleotide variants and haplotypes that showed that the common HHC haplotype was significantly associated with a higher average of CD4&#43; T-cell counts among the Omani HIV-1-infected patients &#40;<span class="elsevierStyleItalic">p</span>&#8239;&#61;&#8239;0&#46;024&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Joshi et al&#46; in 2017 demonstrated that ccr5 promoter polymorphisms correlate with CD4 T cell loss maybe by regulating CD4 T cell apoptosis in HIV patients&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">We found some association between the IL-6 GC polymorphism with values of high viral load above 5000 RNA copies&#47;&#181;L&#46; Previously&#44; Borges et al&#46; found that HIV replication was associated with significantly increased IL-6 levels&#46; There was apparently a dose-response effect with increasing fold differences in IL-6 secretion with higher HIV RNA plasma levels&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In another study&#44; Sherman et al&#46; found forty variants associated with IL-6 levels in the transethnic group&#46; These authors identified that the increased level of IL-6 could be the result of increased levels of sIL-6R &#40;variant rs4133213 related to plasma&#41; as the binding of IL-6 by sIL-6R could protect IL-6 from degradation&#46; When IL-6 binds to sIL-6R&#44; it can trigger the trans-signaling pathway&#44; which is responsible for the pro-inflammatory action of IL-6&#46; These findings support the notion that host genetics contribute to chronic inflammation in HIV individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Also&#44; variability in viral load is influenced by host&#44; viral&#44; and environmental factors&#44; including human genetic variation&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The mechanisms of altered gene expression associated with polymorphisms are still poorly understood&#46; There is evidence that sequence changes in the noncoding regions of cytokine genes may influence the production of the corresponding products&#44; due to linkage with another marker directly affecting gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">When the objective of a study is to identify whether several polymorphisms or variants of genes are related to a disease or not&#44; it must be determined if the genes are in linkage disequilibrium &#40;LD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> This analysis is fundamental to the investigation on genetic architecture of complex traits in human disease&#44; and population structure and evolution dynamics&#46; However&#44; until now&#44; studies primarily focus on LD status between genetic variants located on the same chromosome&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> In this study&#44; the four evaluated genes were located on different chromosomes &#40;e&#46;g&#46;&#44; <span class="elsevierStyleItalic">ccr5</span> &#40;3p21&#46;31&#41;&#44; <span class="elsevierStyleItalic">IL-6</span> &#40;7p15&#46;3&#41;&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> &#40;12q&#46;15&#41; and <span class="elsevierStyleItalic">IL-10</span> &#40;1q32&#46;1&#41;&#41; therefore they segregate independently&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">AIDS is a consequence of the interaction between the individual&#8217;s genetic background and the environmental factors faced by the individual&#44; in which gene-gene interaction may play a significant role&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In this study&#44; only one combination of SNPs shows a highly significant increased risk of HIV infection but with very low frequency &#40;&#60;1&#37;&#41;&#46; However&#44; we cannot conclude that it is really responsible for modifying the risk of the disease&#46; For this&#44; it would be necessary to have information from functional studies that demonstrated a different biological effect compared to the most frequent combination&#46; Further experiments should address this point in the future&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">This study has some limitations&#58; i&#41; the size sample &#40;two groups with 120 patients&#41;&#44; ii&#41; the retrospective and transversal study&#44; iii&#41; the limited number of cytokines polymorphisms evaluated in connection with the HIV-1 infection and iv&#41; the seropositive persons included in the study were under treatment and this could impact on disease progression&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In any case&#44; this study has value in that it is the first&#44; to our knowledge&#44; in reporting genetic profiles of coreceptors and cytokines in patients infected with HIV-1 and patients exposed and not infected&#44; and their influence on susceptibility and disease progression in real life situations in Cuba&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This research received no external funding&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of Interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Institutional review board statement</span><p id="par0170" class="elsevierStylePara elsevierViewall">The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of IPK and HHA for studies involving humans&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Informed consent statement</span><p id="par0175" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all subjects involved in the study&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Genetic studies have shown associations of several single nucleotide polymorphisms &#40;SNP&#41; with different rates of progression and variation in susceptibility to HIV infection&#46; This study aimed to estimate the frequency of ccr5&#916;32&#44; IL-6-174G&#47;C&#44; IFN-&#947;&#43;874T&#47;A and IL-10-1082A&#47;G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine &#171;Pedro Kour&#187; &#40;IPK&#41; and the Ameijeiras Hospital from June 2018 until December 2019&#46; The amplification of fragments of the <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III&#46; Amplification Refractory Mutation System was used for <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The allelic and genotypic distributions of the genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> did not differ significantly between the two groups&#46; Cell counts and plasma viral load values did not differ significantly between genotypes of the <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947;</span> and <span class="elsevierStyleItalic">IL-10</span> genes&#46; Only the IL-6 GC genotype was associated with higher viral load values&#46; The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them&#44; but with a very low frequency &#40;&#60;1&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduccion</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Los estudios gen&#233;ticos han demostrado asociaciones de varios polimorfismos de un solo nucle&#243;tido &#40;SNP&#41; con diferentes tasas de progresi&#243;n y variaci&#243;n en la susceptibilidad a la infecci&#243;n por VIH&#46; Este estudio tuvo como objetivo estimar la frecuencia de los polimorfismos ccr5&#916;32&#44; IL-6-174G&#47;C&#44; IFN-&#947;&#43;874T&#47;A e IL-10-1082A&#47;G en pacientes cubanos infectados por VIH y un grupo de parejas serodiscordantes para evaluar su influencia sobre el riesgo y la progresi&#243;n de la enfermedad&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio transversal en 120 sujetos atendidos en el Instituto de Medicina Tropical &#171;Pedro Kour&#187; &#40;IPK&#41; y el Hospital Hermanos Ameijeiras entre junio de 2018 y diciembre de 2019&#46; La amplificaci&#243;n de los fragmentos de los genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span> se realiz&#243; mediante reacci&#243;n en cadena de la polimerasa seguida por el an&#225;lisis del polimorfismo de fragmentos de restricci&#243;n utilizando la enzima Nla III para la IL-6&#46; El Sistema de Mutaci&#243;n Refractario a la Amplificaci&#243;n por PCR se utiliz&#243; en el caso de los genes <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span>&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Las distribuciones al&#233;licas y genot&#237;picas de los genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span> no difirieron significativamente entre los dos grupos&#46; Los recuentos celulares y los valores de carga viral en plasma no difirieron significativamente entre los genotipos de los genes <span class="elsevierStyleItalic">ccr5</span>&#44; <span class="elsevierStyleItalic">IL-6</span>&#44; <span class="elsevierStyleItalic">IFN-&#947; e IL-10</span>&#46; S&#243;lo el genotipo IL-6 GC se asoci&#243; con valores m&#225;s altos de carga viral&#46; La combinaci&#243;n de alelos de los cuatro SNP considerados mostr&#243; un aumento muy significativo del riesgo de infecci&#243;n por VIH para uno de ellos&#44; pero con una frecuencia muy baja &#40;&#60; 1&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Este estudio contribuye a evaluar la frecuencia de estos polimorfismos y su influencia en los biomarcadores de la progresi&#243;n de la infecci&#243;n por VIH en la poblaci&#243;n cubana con infecci&#243;n por el VIH&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Distribution of HIV-1 plasma viral loads &#40;log10&#41; by the genotypes of the <span class="elsevierStyleItalic">ccr5</span> &#40;a&#41;&#44; <span class="elsevierStyleItalic">IL-6</span> &#40;b&#41;&#44; <span class="elsevierStyleItalic">IL-10</span> &#40;c&#41;&#44; and <span class="elsevierStyleItalic">IFN-&#947;</span> &#40;d&#41; genes in the HIV-1 seropositive group&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Genome location&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primers&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hybridization temperature &#40;&#176;C&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Restriction enzymes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Alleles and fragment &#40;pb&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ccr5</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;174 &#40;promoter&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-GCTCTCTCCCAGGAATCATC-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#176;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deletion &#916;32 pb</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-CGAGAGAGGGTCCTTAGTAG-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-6</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;174&#8239;G&#47;C &#40;promoter&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">IL-6F</span>&#58; 5&#697;-AAGGAAGAGTGGTTCTGCTTCT-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#176;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;Nla III&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&#58; 85&#44; 84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-6R</span>&#58; 5&#697;-ATCTTTGTTGGAGGGTGAGG-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&#58; 169&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IL-10</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;1082&#8239;G&#47;A &#40;promoter&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Primer generic antisense&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
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                  \t\t\t\t">62&#176;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&#58; 550&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-CAGCCCTTCCATTTTACTTTC-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">IL-10G</span>&#58; 5&#697;-TACTAAGGCTTCTTTGGGAG-3&#697;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">IL-10A</span>&#58; 5&#697;-CTACTAAGGCTTCTTTGGGAA-3&#697;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IFN-&#947;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;874&#8239;T&#47;A &#40;promoter&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primer generic antisense&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
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                  \t\t\t\t">56&#176;</td><td class="td" title="\n
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                  \t\t\t\t  " rowspan="6" align="left" valign="\n
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                  \t\t\t\t">ND</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">A&#58; 261&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">5&#697;-TCAACAAAGCTGATACTCCA-3&#697;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">5&#697;-TTCTTACAACACAAAATCAAATCA-3&#697;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">IFN-&#947; T</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#697;-TTCTTACAACACAAAATCAAATCT-3&#697;&nbsp;\t\t\t\t\t\t\n
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                  <table border="0" frame="\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients n&#8239;&#61;&#8239;61</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients n&#8239;&#61;&#8239;59</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of persons&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of persons&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>20&#8211;29 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9999</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>30&#8211;39 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>40&#8211;49 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>50&#8211;59 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>60 years and more&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gender</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;0001<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Color of skin</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>White&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;1399</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Black&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mestize&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sexual orientation</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Homosexual&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t" scope="col">Genotypes and alleles&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">HIV-1 seropositive patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Genotype <span class="elsevierStyleItalic">IL-6</span> G&#47;G&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">42&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;4700 &#40;0&#46;6661&#8211;3&#46;2440&#41;</td><td class="td" title="\n
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                  \t\t\t\t  " rowspan="3" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype C&#47;C&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;8259 &#40;0&#46;4113&#8211;1&#46;658&#41;</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;6012</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">1&#46;5000 &#40;0&#46;3131&#8211;7&#46;1856&#41;</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype G&#47;A&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Genotype G&#47;G&nbsp;\t\t\t\t\t\t\n
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Original language: English
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