Details

Autor(en) / Beteiligte

• Troyer, Jennifer L.
• Nelson, George W.
• Lautenberger, James A.
• Chinn, Leslie
• McIntosh, Carl
• Johnson, Randall C.
• Sezgin, Efe
• Kessing, Bailey
• Malasky, Michael
• Hendrickson, Sher L.
• Li, Guan
• Pontius, Joan
• Tang, Minzhong
• An, Ping
• Winkler, Cheryl A.
• Limou, Sophie
• Le Clerc, Sigrid
• Delaneau, Olivier
• Zagury, Jean-François
• Schuitemaker, Hanneke
• van Manen, Daniëlle
• Bream, Jay H.
• Gomperts, Edward D.
• Buchbinder, Susan
• Goedert, James J.
• Kirk, Gregory D.
• O'Brien, Stephen J.

Titel

Genome-Wide Association Study Implicates PARD3B-Based AIDS Restriction

Ist Teil von

• The Journal of infectious diseases, 2011-05, Vol.203 (10), p.1491-1502

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2011

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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⁻ɸ). 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.