Biology Faculty Articles

Title

Behavioral Risk Exposure and Host Genetics of Susceptibility to HIV-1 Infection

Document Type

Article

Publication Date

1-1-2006

Publication Title

Journal of Infectious Diseases

ISSN

0022-1899

Volume

193

Issue/No.

1

First Page

16

Last Page

26

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.

Comments

©2005 by the Infectious Diseases Society of America. All rights reserved.

Additional Comments

National Cancer Institute contract #: N01-CO-12400; National Institute on Drug Abuse grant #s: DA09225, DA8009, DA12568

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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