The rs2231142 variant of the ABCG2 gene is associated with uric acid levels and gout among Japanese people

Rheumatology (Oxford). 2010 Aug;49(8):1461-5. doi: 10.1093/rheumatology/keq096. Epub 2010 Apr 25.


Objectives: Recent genome-wide association and functional studies have shown that the ABCG2 gene encodes for a urate transporter, and a common causal ABCG2 variant, rs2231142, leads to elevated uric acid levels and prevalent gout among Whites and Blacks. We examined whether this finding is observed in a Japanese population, since Asians have a high reported prevalence of the T-risk allele.

Methods: A total of 3923 Japanese people from the Circulatory Risk in Communities Study aged 40-90 years were genotyped for rs2231142. Associations of the rs2231142 variant with serum uric acid levels and prevalence of gout and hyperuricaemia were examined.

Results: The frequency of the T-risk allele was 31% in this Japanese sample. Multivariable adjusted mean uric acid levels were 7-9 micromol/l higher for TG and TT than GG carriers (P-additive = 0.0006). The multivariable-adjusted odds ratio (OR) of prevalent gout was 1.37 (95% CI 0.68, 2.76) for TG and 4.37 (95% CI 1.98, 9.62) for TT compared with the GG carriers (P-additive = 0.001). When evaluating the combined outcome of hyperuricaemia and gout, the respective ORs were 1.40 (95% CI 1.04, 1.87) for TG and 1.88 (95% CI 1.23, 2.89) for TT carriers. The population attributable risk was 29% for gout and 19% for gout and/or hyperuricaemia.

Conclusions: The association of the causal ABCG2 rs2231142 variant with uric acid levels and gout was confirmed in a sample of Japanese ancestry. Our study emphasizes the importance of this common causal variant in a population with a high risk allele frequency, especially as more Japanese adopt a Western lifestyle with a concomitant increase in mean serum uric acid levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Gout / genetics*
  • Gout / metabolism
  • Humans
  • Hyperuricemia / genetics*
  • Hyperuricemia / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Polymorphism, Single Nucleotide
  • Uric Acid / blood*


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins
  • Organic Anion Transporters
  • urate transporter
  • Uric Acid