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Article
Behavioral Risk Exposure and Host Genetics of Susceptibility to HIV-1 Infection
Journal of Infectious Diseases
  • 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 Frederick
  • Matthew W. Smith, National Cancer Institute at Frederick
Document Type
Article
Publication Date
1-1-2006
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
Citation Information
Sadeep Shrestha, Steffanie A. Strathdee, Noya Galai, T. K. Oleksyk, et al.. "Behavioral Risk Exposure and Host Genetics of Susceptibility to HIV-1 Infection" Journal of Infectious Diseases Vol. 193 Iss. 1 (2006) p. 16 - 26 ISSN: 0022-1899
Available at: http://works.bepress.com/stephen-obrien/21/