Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population.
Sci Transl Med
; 1(5): 5ra11, 2009 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-20368174
ABSTRACT
Gout based on hyperuricemia is a common disease with a genetic predisposition, which causes acute arthritis. The ABCG2/BCRP gene, located in a gout-susceptibility locus on chromosome 4q, has been identified by recent genome-wide association studies of serum uric acid concentrations and gout. Urate transport assays demonstrated that ABCG2 is a high-capacity urate secretion transporter. Sequencing of the ABCG2 gene in 90 hyperuricemia patients revealed several nonfunctional ABCG2 mutations, including Q126X. Quantitative trait locus analysis of 739 individuals showed that a common dysfunctional variant of ABCG2, Q141K, increases serum uric acid. Q126X is assigned to the different disease haplotype from Q141K and increases gout risk, conferring an odds ratio of 5.97. Furthermore, 10% of gout patients (16 out of 159 cases) had genotype combinations resulting in more than 75% reduction of ABCG2 function (odds ratio, 25.8). Our findings indicate that nonfunctional variants of ABCG2 essentially block gut and renal urate excretion and cause gout.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transportadores de Cassetes de Ligação de ATP
/
Genética Populacional
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Gota
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Mutação
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Sci Transl Med
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão