Toll-like receptor polymorphism associations with HIV-1 outcomes among sub-Saharan Africans

J Infect Dis. 2014 May 15;209(10):1623-7. doi: 10.1093/infdis/jit807. Epub 2013 Dec 10.

Abstract

Objective: We evaluated Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and disease progression in African couples.

Methods: Seven candidate and 116 haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and 343 seronegative controls.

Results: TLR9 1635A/G was associated with reduced HIV-1 acquisition among HIV-seronegative controls with high but not low HIV-1 exposure (odds ratio [OR] = 0.7; P = .03 and OR = 0.9, P = .5, respectively). TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time since HIV-1 acquisition. TLR8 1A/G reduced disease progression.

Conclusions: TLR SNPs impact HIV-1 outcomes with epidemiologic factors modifying these relationships.

Keywords: Acute Infection; Genetics; HIV-1 acquisition; HIV-1 set-point; Heterosexual HIV-1 transmission; Progression; Risk Factors; Toll-like Receptors; Viral load.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa South of the Sahara / epidemiology
  • Anti-HIV Agents / therapeutic use*
  • Evolution, Molecular
  • Genetic Variation
  • HIV Infections / genetics*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1
  • Humans
  • Mutation
  • Phylogeny
  • RNA, Viral / cerebrospinal fluid
  • Toll-Like Receptors / genetics*
  • Viral Load
  • Virus Replication

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Toll-Like Receptors