Genetic impact on uric acid concentration and hyperuricemia in the Japanese population

J Atheroscler Thromb. 2013;20(4):351-67. doi: 10.5551/jat.15727. Epub 2012 Dec 13.


Aim: Using general Japanese populations, we performed a replication study of genetic loci previously identified in European-descent populations as being associated with uric acid and gout. The relative contribution of non-genetic and genetic factors to the variances in serum uric acid concentration was then evaluated.

Methods: Seven single nucleotide polymorphisms (SNPs) were genotyped from 7 candidate loci robustly confirmed in Europeans. Genotyping was performed in up to 17,226 individuals, from which 237 hyperuricemia cases and 3,218 controls were chosen for a case-control study. For 6 SNPs showing a replication of uric acid association in 17,076 general population samples, we further tested the associations with other metabolic traits (n≤5,745) and with type 2 diabetes (931 cases and 1404 controls) and coronary artery disease (806 cases and 1337 controls).

Results: Significant uric acid associations (one-tailed p<0.05) were replicated for 6 loci in Japanese. The strongest association was detected at SLC22A12 rs505802 for uric acid (p=2.4×10(-50)) and ABCG2 rs2231142 for hyperuricemia (p3.6×10(-10)). The combined genetic effect could explain some proportion of inter-individual variation in uric acid (R(2)=0.03) and was more or less comparable to the effect of well-recognized risk factors -BMI (R(2)=0.04) and alcohol intake (R(2)=0.01). The tested SNPs were not significantly associated with cardiovascular risk traits except for GCKR rs780094.

Conclusion: Our results confirm that 6 common uric acid variant loci are reproducible in Japanese. Further investigation is warranted to efficiently use the knowledge about genetic factors in combination with modifiable risk factors when we decide an individual's treatment strategy for hyperuricemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics*
  • Coronary Disease / genetics
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Humans
  • Hyperuricemia / genetics*
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Uric Acid / blood*


  • Uric Acid