Biology Faculty Articles

Title

Genome-Wide Association Study Implicates PARD3B-Based AIDS Restriction

Document Type

Article

Publication Date

5-15-2011

Publication Title

Journal of Infectious Diseases

ISSN

0022-1899

Volume

203

Issue/No.

10

First Page

1491

Last Page

1502

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.

Comments

©Oxford University Press on behalf of the Infectious Diseases Society of America 2011.

Additional Comments

National Cancer Institute contract #: HHSN26120080001E; National Institute of Child Health and Human Development grant #: 1 R01 HD41224; Netherlands Organization for Scientific Research grant #: 9120.6046

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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