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

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

SUBMITTER: Troyer JL

PROVIDER: S-EPMC3080910 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Troyer Jennifer L JL Nelson George W GW Lautenberger James A JA Chinn Leslie L McIntosh Carl C Johnson Randall C RC Sezgin Efe E Kessing Bailey B Malasky Michael M Hendrickson Sher L SL Li Guan G Pontius Joan J Tang Minzhong M An Ping P Winkler Cheryl A CA Limou Sophie S Le Clerc Sigrid S Delaneau Olivier O Zagury Jean-François JF Schuitemaker Hanneke H van Manen Daniëlle D Bream Jay H JH Gomperts Edward D ED Buchbinder Susan S Goedert James J JJ Kirk Gregory D GD O'Brien Stephen J SJ

The Journal of infectious diseases 20110501 10

<h4>Background</h4>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.<h4>Methods</h4>European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proporti ...[more]

PMID: 21502085

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

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

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