title: Immunogenetic influences on acquisition of HIV-1 infection: consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2).
abstract: Numerous reports have suggested that immunogenetic factors may influence human immunodeficiency virus (HIV)-1 acquisition, yet replicated findings that translate between study cohorts remain elusive. Our work aimed to test several hypotheses about genetic variants within the IL10-IL24 gene cluster that encodes interleukin (IL)-10, IL-19, IL-20 and IL-24. In aggregated data from 515 Rwandans and 762 Zambians with up to 12 years of follow-up, 190 single-nucleotide polymorphisms passed quality control procedures. When HIV-1-exposed seronegative subjects (n=486) were compared with newly seroconverted individuals (n=313) and seroprevalent subjects (n=478) who were already infected at enrollment, rs12407485 (G>A) in IL19 showed a robust association signal in adjusted logistic regression models (odds ratio=0.64, P=1.7 × 10(-4) and q=0.033). Sensitivity analyses demonstrated that (i) results from both cohorts and subgroups within each cohort were highly consistent; (ii) verification of HIV-1 infection status after enrollment was critical; and (iii) supporting evidence was readily obtained from Cox proportional hazards models. Data from public databases indicate that rs12407485 is part of an enhancer element for three transcription factors. Overall, these findings suggest that molecular features at the IL19 locus may modestly alter the establishment of HIV-1 infection.
authors: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: X
authors: X
authors: Li
authors: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: K
authors: K
authors: Zhang
authors: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors: N M
authors: NM
authors: Pajewski
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: I
authors: I
authors: Brill
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: H A
authors: HA
authors: Prentice
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: S
authors: S
authors: Shrestha
authors: Zambia-Emory HIV-1 Research Project, Lusaka, Zambia.
authors: W
authors: W
authors: Kilembe
authors: Project San Francisco, Kigali, Rwanda.
authors: E
authors: E
authors: Karita
authors: 1] Project San Francisco, Kigali, Rwanda [2] Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
authors: S
authors: S
authors: Allen
authors: Emory Vaccine Center, Emory University, Atlanta, GA, USA.
authors: E
authors: E
authors: Hunter
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: R A
authors: RA
authors: Kaslow
authors: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: J
authors: J
authors: Tang
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People; D002878:Chromosomes, Human, Pair 1; D015331:Cohort Studies; D019295:Computational Biology; D004198:Disease Susceptibility; D004742:Enhancer Elements, Genetic; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C421250:IL19 protein, human; D007378:Interleukins
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