TY - JOUR

T1 - Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa

AU - Xie, Wen

AU - Agniel, Denis

AU - Shevchenko, Andrey

AU - Malov, Sergey V.

AU - Svitin, Anton

AU - Cherkasov, Nikolay

AU - Baum, Marianna K.

AU - Campa, Adriana

AU - Gaseitsiwe, Simani

AU - Bussmann, Hermann

AU - Makhema, Joseph

AU - Marlink, Richard

AU - Novitsky, Vladimir

AU - Lee, Tun Hou

AU - Cai, Tianxi

AU - O'Brien, Stephen J.

AU - Essex, M.

N1 - Publisher Copyright: © 2017, Mary Ann Liebert, Inc. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

KW - HIV clinical outcomes research

KW - HIV transmission

KW - HIV/AIDS pathogenesis

KW - natural hosts

KW - Restriction factors

UR - http://www.scopus.com/inward/record.url?scp=85020469197&partnerID=8YFLogxK

U2 - 10.1089/aid.2016.0017

DO - 10.1089/aid.2016.0017

M3 - Article

C2 - 28132517

AN - SCOPUS:85020469197

VL - 33

SP - 596

EP - 609

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

SN - 0889-2229

IS - 6

ER -