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See Latest ArticlesIdentification of a urate transporter, ABCG2, with a common functional polymorphism causing gout
Proceedings of the National Academy of Sciences of the United States of America, 06/30/09
Woodward OM et al. – Data suggest that at least 10% of all gout cases in whites are attributable to common SNP rs2231142 in ATP-binding cassette, subfamily G, 2 (ABCG2) gene. With approximately 3 million US individuals suffering from often insufficiently treated gout, ABCG2 represents an attractive drug target.
Methods- GWAS to identify SNPs in a genomic region on chromosome 4 that associate with serum urate levels and gout, a consequence of elevated urate levels
- Functional assays showed that human ABCG2, encoded by the ABCG2 gene is a urate efflux transporter
- Native ABCG2 is located in the brush border membrane of kidney proximal tubule cells, where it mediates renal urate secretion
- Introduction of the mutation Q141K encoded by the common SNP rs2231142 resulted in 53% reduced urate transport rates vs wild-type
- Data from a population-based study of 14,783 individuals support rs2231142 as the causal variant in this region
- It shows highly significant associations with urate levels and gout
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