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AIDS Res Hum Retroviruses. 2017 Jan 28. doi: 10.1089/AID.2016.0017. [Epub ahead of print]

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

Author information

  • 1Boston, United States ; xiew06@gmail.com.
  • 2Boston, United States ; denis_agniel@hms.harvard.edu.
  • 3St Petersburg, Russian Federation ; andrey.k.shevchenko@gmail.com.
  • 4St Petersburg, Russian Federation ; malovs@sm14820.spb.edu.
  • 5St. Petersburg, Russian Federation ; anton.svitin@gmail.com.
  • 6St. Petersburg, Russian Federation ; nikolay@cherkasov.spb.ru.
  • 7Florida International University, College of Public Health , University Park , 11200 SW 8th Street , Miami, Florida, United States , 33199 ; baumm@fiu.edu.
  • 8FIU, Diet and Nutrition , HLS-1-337 , University Park , Miami, Florida, United States , 33199 ; campaa@fiu.edu.
  • 9Botswana Harvard AIDS Institution Partnership, Research Lab , Private Bag BO320 , Gaborone , Gaborone, Botswana ; sgaseitsiwe@bhp.org.bw.
  • 10Botswana Harvard AIDS Institution Partnership, Research Lab, Gaborone, Botswana ; hermann.bussmann@gmail.com.
  • 11Botswana Harvard AIDS Institution Partnership, Research Lab, Gaborone, Botswana ; jmakhema@bhp.org.bw.
  • 12Harvard School of Public Health, IID , 651 Huntington Avenue , FXB, 631 , Boston, Massachusetts, United States , 02115 ; marlink@hsph.harvard.edu.
  • 13HSPH, Immunology & Infectious Diseases , FXB-310, 651 Huntington Avenue , Boston, Massachusetts, United States , 02115 ; vnovi@hsph.harvard.edu.
  • 14Harvard School of Public Health, IID, Boston, Massachusetts, United States ; tunhoule@hsph.harvard.edu.
  • 15Harvard School of Public Health, Biostatistics, Boston, Massachusetts, United States ; tcai@hsph.harvard.edu.
  • 16St. Petersburg, Russian Federation ; lgdchief@gmail.com.
  • 17Harvard School of Public Health, Immunology and Infectious Diseases , FXB 402 , 651 Huntington Ave , Boston, Massachusetts, United States , 02115 ; messex@hsph.harvard.edu.

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 GWAS on a total of 556treatment-naive HIV-infected individuals in Botswana. We characterized the pattern of HIV disease progression using a novel functional principal component analysis (fPCA) which can better capture longitudinal CD4 and viral load (VL)trajectories. Two SNPs near HCG22 (chr 6, peak variant rs2535307, combined P = 3.72×10-7, minor allele as risky allele)and CCNG1 (chr 5, 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.

PMID:
28132517
DOI:
10.1089/AID.2016.0017
[PubMed - as supplied by publisher]
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