Document Detail


Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand M??ori, Pacific Island, and Caucasian case-control sample sets.
MedLine Citation:
PMID:  19877038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of M??ori, Pacific Island, and Caucasian ancestry and to determine if the M??ori and Pacific Island samples could be useful for fine-mapping. METHODS: Patients (n= 56 M??ori, 69 Pacific Island, and 131 Caucasian) were recruited from rheumatology outpatient clinics and satisfied the American College of Rheumatology criteria for gout. The control samples comprised 125 M??ori subjects, 41 Pacific Island subjects, and 568 Caucasian subjects without arthritis. SLC2A9 single-nucleotide polymorphisms rs16890979 (V253I), rs5028843, rs11942223, and rs12510549 were genotyped (possible etiologic variants in Caucasians). RESULTS: Association of the major allele of rs16890979, rs11942223, and rs5028843 with gout was observed in all sample sets (P = 3.7 x 10(-7), 1.6 x 10(-6), and 7.6 x 10(-5) for rs11942223 in the M??ori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the M??ori and Pacific Island control samples) was not observed in a single gout case. CONCLUSION: Our data confirm a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set, with the effect on risk (odds ratio >2.0) greater than previous estimates. We also demonstrate association of SLC2A9 with gout in samples of M??ori and Pacific Island ancestry and a consistent pattern of haplotype association. The presence of both alleles of rs16890979 on susceptibility and protective haplotypes in the M??ori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in M??ori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping.
Authors:
Jade E Hollis-Moffatt; Xin Xu; Nicola Dalbeth; Marilyn E Merriman; Ruth Topless; Chloe Waddell; Peter J Gow; Andrew A Harrison; John Highton; Peter B B Jones; Lisa K Stamp; Tony R Merriman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  60     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-10     Completed Date:  2010-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3485-92     Citation Subset:  AIM; IM    
Affiliation:
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Case-Control Studies
Ethnic Groups / ethnology,  genetics
European Continental Ancestry Group / ethnology,  genetics*
Female
Genetic Predisposition to Disease / genetics*
Glucose Transport Proteins, Facilitative / genetics*
Gout / ethnology,  genetics*
Haplotypes / genetics
Humans
Linkage Disequilibrium / genetics
Male
Middle Aged
New Zealand
Oceanic Ancestry Group / ethnology,  genetics*
Organic Anion Transporters / genetics*
Pacific Islands
Polymorphism, Single Nucleotide / genetics*
Young Adult
Chemical
Reg. No./Substance:
0/Glucose Transport Proteins, Facilitative; 0/Organic Anion Transporters; 0/SLC2A9 protein, human; 0/urate transporter

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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