Behavioral Risk Exposure and Host Genetics of Susceptibility to HIV-1 Infection
Journal of Infectious Diseases
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.
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.
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.
Our results suggest that genetic variants in associated host genes may play an important role in susceptibility to HIV-1 infection.
Shrestha, Sadeep; Steffanie A. Strathdee; Noya Galai; T. K. Oleksyk; M. Daniele Fallin; Shruti Mehta; Daniel Schaid; David Vlahov; Stephen J. O'Brien; and Matthew W. Smith. 2006. "Behavioral Risk Exposure and Host Genetics of Susceptibility to HIV-1 Infection." Journal of Infectious Diseases 193, (1): 16-26. http://nsuworks.nova.edu/cnso_bio_facarticles/532