Title

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

Authors

Sadeep Shrestha, National Cancer Institute at Frederick; Johns Hopkins University
Steffanie A. Strathdee, Johns Hopkins University; University of California - San Diego
Noya Galai, Johns Hopkins University
T. K. Oleksyk, National Cancer Institute at Frederick
M. Daniele Fallin, Johns Hopkins University
Shruti Mehta, Johns Hopkins University
Daniel Schaid, Mayo Clinic College of Medicine
David Vlahov, New York Academy of Medicine
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Matthew W. Smith, National Cancer Institute at Frederick

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

NSUWorks Citation

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. https://nsuworks.nova.edu/cnso_bio_facarticles/532

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015