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.
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This work was supported primarily by the National Institute of Allergy and Infectious Disease through R01 AI071906 (and its supplemental award) to RAK/JT and R01 AI064060 to EH. SA and EH received additional funding from the International AIDS Vaccine Initiative (Protocol C), with further support (UL1 RR025008) from the Clinical Translational Science Award program, National Center for Research Resources. We are grateful to members of the Rwanda–Zambia HIV-1 Research Group for their valuable contributions to patient enrollment. We also thank Paul Farmer, Naw Htee Khu, Hailin Lu and Travis R Porter for their assistance with sample inventories, genotyping and data management.
The authors declare no conflict of interest.
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Li, X., Zhang, K., Pajewski, N. et al. Immunogenetic influences on acquisition of HIV-1 infection: consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2). Genes Immun 16, 213–220 (2015). https://doi.org/10.1038/gene.2014.84