Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa

Wen Xie, Denis Agniel, Andrey Shevchenko, Sergey V. Malov, Anton Svitin, Nikolay Cherkasov, Marianna K. Baum, Adriana Campa, Simani Gaseitsiwe, Hermann Bussmann, Joseph Makhema, Richard Marlink, Vladimir Novitsky, Tun Hou Lee, Tianxi Cai, Stephen J. O'Brien, M. Essex

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Sub-Saharan Africans infected with HIV-1C make up the largest AIDS patient population in the world and exhibit large heterogeneity in disease progression before initiating antiretroviral therapy. To identify host variants associated with HIV disease progression, we performed genome-wide association studies on a total of 556 treatment-naive HIV-infected individuals in Botswana. We characterized the pattern of HIV disease progression using a novel functional principal component analysis, which can better capture longitudinal CD4 and viral load (VL) trajectories. Two single-nucleotide polymorphisms (SNPs) near HCG22 (chr6, peak variant rs2535307, combined p = 3.72 × 10-7, minor allele as risky allele) and CCNG1 (chr5, peak variant kgp22385164, combined p = 1.88 × 10-6, minor allele as risky allele) were significantly associated with CD4 and VL dynamics. Inspection of SNPs in these gene regions in a third Botswana cohort (using GWATCH) also revealed a strong association of HCG22 with HIV-1C acquisition, suggesting that this region is associated with infection as well as disease progression. Our study uncovered two genetic regions that are significant and have specific effects on HIV-1C acquisition or progression in sub-Saharan Africans, and the result suggested new potential targets for AIDS prevention and treatment. In addition, our results also indicate the possibility of using genetic markers as HIV disease progression indicators in sub-Saharan Africans to prioritize fast progressors for antiretroviral treatment.

Original languageEnglish (US)
Pages (from-to)596-609
Number of pages14
JournalAIDS research and human retroviruses
Volume33
Issue number6
DOIs
StatePublished - Jun 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology
  • Infectious Diseases

Keywords

  • HIV clinical outcomes research
  • HIV transmission
  • HIV/AIDS pathogenesis
  • Restriction factors
  • natural hosts

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