Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection

Sadeep Shrestha, Steffanie A. Strathdee, Noya Galai, Taras Oleksyk, M. Daniele Fallin, Shruti Mehta, Daniel J Schaid, David Vlahov, Stephen J. O'Brien, Michael W. Smith

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)16-26
Number of pages11
JournalJournal of Infectious Diseases
Volume193
Issue number1
DOIs
StatePublished - Jan 1 2006

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Virus Diseases
Genetic Predisposition to Disease
HIV-1
Haplotypes
Interleukin-2
Single Nucleotide Polymorphism
Case-Control Studies
Logistic Models
Genes
Chemokine CCL5
Genetic Models
Risk-Taking
African Americans
Interleukin-10
Acquired Immunodeficiency Syndrome
Regression Analysis
Infection

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Shrestha, S., Strathdee, S. A., Galai, N., Oleksyk, T., Fallin, M. D., Mehta, S., ... Smith, M. W. (2006). Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection. Journal of Infectious Diseases, 193(1), 16-26. https://doi.org/10.1086/498532

Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection. / Shrestha, Sadeep; Strathdee, Steffanie A.; Galai, Noya; Oleksyk, Taras; Fallin, M. Daniele; Mehta, Shruti; Schaid, Daniel J; Vlahov, David; O'Brien, Stephen J.; Smith, Michael W.

In: Journal of Infectious Diseases, Vol. 193, No. 1, 01.01.2006, p. 16-26.

Research output: Contribution to journalArticle

Shrestha, S, Strathdee, SA, Galai, N, Oleksyk, T, Fallin, MD, Mehta, S, Schaid, DJ, Vlahov, D, O'Brien, SJ & Smith, MW 2006, 'Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection', Journal of Infectious Diseases, vol. 193, no. 1, pp. 16-26. https://doi.org/10.1086/498532
Shrestha S, Strathdee SA, Galai N, Oleksyk T, Fallin MD, Mehta S et al. Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection. Journal of Infectious Diseases. 2006 Jan 1;193(1):16-26. https://doi.org/10.1086/498532
Shrestha, Sadeep ; Strathdee, Steffanie A. ; Galai, Noya ; Oleksyk, Taras ; Fallin, M. Daniele ; Mehta, Shruti ; Schaid, Daniel J ; Vlahov, David ; O'Brien, Stephen J. ; Smith, Michael W. / Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection. In: Journal of Infectious Diseases. 2006 ; Vol. 193, No. 1. pp. 16-26.
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