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J Infect Dis. 2011 May 15;203(10):1491-502. doi: 10.1093/infdis/jir046.

Genome-wide association study implicates PARD3B-based AIDS restriction.

Author information

1
Laboratory of Genomic Diversity, SAIC-Frederick, Inc., Frederick, MD 21702, USA. troyerj@mail.nih.gov

Abstract

BACKGROUND:

Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression.

METHODS:

European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model).

RESULTS:

Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10(-9)) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10(-8)). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025).

CONCLUSIONS:

These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression.

PMID:
21502085
PMCID:
PMC3080910
DOI:
10.1093/infdis/jir046
[Indexed for MEDLINE]
Free PMC Article

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