Behavioral risk exposure and host genetics of susceptibility to HIV-1 infection.
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.
Shrestha
Sadeep
S
Laboratory of Genomic Diversity, National Cancer Institute at Frederick, National Institutes of Health, MD 21702, USA.
Strathdee
Steffanie A
SA
Galai
Noya
N
Oleksyk
Taras
T
Fallin
M Daniele
MD
Mehta
Shruti
S
Schaid
Daniel
D
Vlahov
David
D
O'Brien
Stephen J
SJ
Smith
Michael W
MW
D000328:Adult; D044383:Black People; D016022:Case-Control Studies; D054407:Chemokine CCL4; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000175:diagnosis / Q000235:genetics*; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D012044:Regression Analysis; D018570:Risk Assessment; D012309:Risk-Taking; D001741:Black or African American
C515334:CCR2 protein, human; D054407:Chemokine CCL4; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine