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Immunogenetic influences on acquisition of HIV-1 infection: consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2)

Genes & Immunity volume 16, pages 213–220 (2015)Cite this article

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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.

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Acknowledgements

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.

Author information

Author notes

  1. H A Prentice

    Present address: 9Current address: Inova Fairfax Hospital, Falls Church, VA, USA.,

  2. R A Kaslow

    Present address: 10Current address: Department of Veterans Affairs, Washington, DC, USA.,

Authors and Affiliations

  1. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    X Li

  2. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    K Zhang & J Tang

  3. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

    N M Pajewski

  4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    I Brill, H A Prentice, S Shrestha & R A Kaslow

  5. Zambia-Emory HIV-1 Research Project, Lusaka, Zambia

    W Kilembe

  6. Project San Francisco, Kigali, Rwanda

    E Karita & S Allen

  7. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA

    S Allen

  8. Emory Vaccine Center, Emory University, Atlanta, GA, USA

    E Hunter

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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

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