Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection.

Academic Article

Abstract

  • BACKGROUND: Some individuals are readily infected with low human immunodeficiency virus type 1 (HIV-1) exposure, whereas others appear less susceptible, suggesting that host genetics plays a role in the viral entry pathway. The matched case-control study design with measured risk exposures provides an avenue for discovering genes involved in susceptibility to infection. METHODS: We conducted a nested case-control study of African Americans (266 HIV-1 seroconverter cases and 532 seronegative controls from the AIDS Link to Intravenous Experience cohort), to examine the association between 50 single-nucleotide polymorphisms (SNPs) in 9 candidate genes (CCR5, CCR2, RANTES, MIP1A, MCP2, IL10, IFNG, MCSF, and IL2) and susceptibility to HIV-1 infection. To account for differential exposure propensities, risk behavior self-reported during semiannual visits was used to estimate a standardized cumulative risk exposure (SCRE). Individual SNPs were evaluated using conditional logistic-regression models, and the inferred haplotypes were assessed in the haplotype trend regression analyses after adjusting for age and SCRE. RESULTS: Four SNPs (CCR2-V64I, CCR5-2459, MIP1A+954, and IL2+3896) and specific haplotypes in the IL2 and CCR2/CCR5 regions were significantly associated with HIV-1 infection susceptibility in different genetic models. CONCLUSIONS: Our results suggest that genetic variants in associated host genes may play an important role in susceptibility to HIV-1 infection.
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    Keywords

  • Adult, African Continental Ancestry Group, Case-Control Studies, Chemokine CCL4, Female, Genetic Predisposition to Disease, HIV Infections, HIV-1, Haplotypes, Humans, Interleukin-2, Macrophage Inflammatory Proteins, Male, Polymorphism, Single Nucleotide, Receptors, CCR2, Receptors, CCR5, Receptors, Chemokine, Regression Analysis, Risk Assessment, Risk-Taking
  • Digital Object Identifier (doi)

    Authorlist

  • Shrestha S; Strathdee SA; Galai N; Oleksyk T; Fallin MD; Mehta S; Schaid D; Vlahov D; O'Brien SJ; Smith MW
  • Start Page

  • 16
  • End Page

  • 26
  • Volume

  • 193
  • Issue

  • 1