| Genome-wide association study implicates PARD3B-based AIDS restriction. | |
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MedLine Citation:
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PMID: 21502085 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jennifer L Troyer; George W Nelson; James A Lautenberger; Leslie Chinn; Carl McIntosh; Randall C Johnson; Efe Sezgin; Bailey Kessing; Michael Malasky; Sher L Hendrickson; Guan Li; Joan Pontius; Minzhong Tang; Ping An; Cheryl A Winkler; Sophie Limou; Sigrid Le Clerc; Olivier Delaneau; Jean-François Zagury; Hanneke Schuitemaker; Daniëlle van Manen; Jay H Bream; Edward D Gomperts; Susan Buchbinder; James J Goedert; Gregory D Kirk; Stephen J O'Brien |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 203 ISSN: 1537-6613 ISO Abbreviation: J. Infect. Dis. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-19 Completed Date: 2011-06-30 Revised Date: 2012-05-15 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: United States |
Other Details:
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Languages: eng Pagination: 1491-502 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Genomic Diversity, SAIC-Frederick, Inc., Frederick, MD 21702, USA. troyerj@mail.nih.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acquired Immunodeficiency Syndrome
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metabolism*,
pathology Carrier Proteins / genetics*, metabolism* Chromosome Mapping Disease Progression Gene Expression Regulation / immunology* Genome, Human Humans Membrane Proteins / genetics*, metabolism* Polymorphism, Single Nucleotide* |
| Grant Support | |
ID/Acronym/Agency:
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1 R01 HD41224/HD/NICHD NIH HHS; HHSN26120080001E//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Membrane Proteins; 0/PARD3B protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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