Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study

PLoS One. 2008;3(12):e3907. doi: 10.1371/journal.pone.0003907. Epub 2008 Dec 24.

Abstract

Previous studies of the HIV-1 disease have shown that HLA and Chemokine receptor genetic variants influence disease progression and early viral load. We performed a Genome Wide Association study in a cohort of 605 HIV-1-infected seroconverters for detection of novel genetic factors that influence plasma HIV-RNA and cellular HIV-DNA levels. Most of the SNPs strongly associated with HIV-RNA levels were localised in the 6p21 major histocompatibility complex (MHC) region and were in the vicinity of class I and III genes. Moreover, protective alleles for four disease-associated SNPs in the MHC locus (rs2395029, rs13199524, rs12198173 and rs3093662) were strikingly over-represented among forty-five Long Term HIV controllers. Furthermore, we show that the HIV-DNA levels (reflecting the HIV reservoir) are associated with the same four SNPs, but also with two additional SNPs on chromosome 17 (rs6503919; intergenic region flanked by the DDX40 and YPEL2 genes) and chromosome 8 (rs2575735; within the Syndecan 2 gene). Our data provide evidence that the MHC controls both HIV replication and HIV reservoir. They also indicate that two additional genomic loci may influence the HIV reservoir.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology
  • Cohort Studies
  • DNA, Viral / metabolism*
  • Disease Progression
  • Female
  • Gene Frequency
  • Genome-Wide Association Study
  • HIV Infections / blood*
  • HIV Infections / genetics*
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / genetics*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci / physiology*
  • RNA, Viral / blood*

Substances

  • DNA, Viral
  • RNA, Viral