TY - JOUR
T1 - Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection
AU - Shrestha, Sadeep
AU - Strathdee, Steffanie A.
AU - Galai, Noya
AU - Oleksyk, Taras
AU - Fallin, M. Daniele
AU - Mehta, Shruti
AU - Schaid, Daniel
AU - Vlahov, David
AU - O'Brien, Stephen J.
AU - Smith, Michael W.
N1 - Funding Information:
Financial support: This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research. This publication has been funded, in part, with federal funds from the NCI, NIH (contract N01-CO-12400), and National Institute on Drug Abuse (grants DA09225, DA8009, and DA12568).
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=29744449044&partnerID=8YFLogxK
U2 - 10.1086/498532
DO - 10.1086/498532
M3 - Article
C2 - 16323127
AN - SCOPUS:29744449044
SN - 0022-1899
VL - 193
SP - 16
EP - 26
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -
