Association of four genetic loci with uric acid levels and reduced renal function: The J-SHIPP Suita study

Yasuharu Tabara, Katsuhiko Kohara, Ryuichi Kawamoto, Yumiko Hiura, Kunihiro Nishimura, Takayuki Morisaki, Yoshihiro Kokubo, Tomonori Okamura, Hitonobu Tomoike, Naoharu Iwai, Tetsuro Miki

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: Recent genome-wide association studies have identified several genetic variants as susceptibility loci for serum uric acid (UA) levels. We also identified a common nonsense mutation, W258X, responsible for renal hypouricemia. Here, we investigated clinical implications of these genetic variants by cross-sectional and longitudinal genetic epidemiological analysis. Methods: The study enrolled 5,165 Japanese subjects aged 64 ± 12 years from the general population. Clinical parameters were obtained from the personal health records, evaluated at medical checkups. Results: Serum UA levels were significantly different between the SLC22A12 rs11231825 (CC/CT/TT: 4.5 ± 1.6, 5.0 ± 1.4, 5.3 ± 1.4 mg/dl; p = 7.6 × 10 -20), SLC2A9 rs1014290 (TT/TG/GG: 4.9 ± 1.4, 5.1 ± 1.4, 5.3 ± 1.4 mg/dl; p = 3.1 × 10-11) and ABCG2 rs2231142 (TT/TG/GG: 5.3 ± 1.5, 5.2 ± 1.4, 5.1 ± 1.4 mg/dl; p = 2.0 × 10-5) genotypes. During 9.4 years of follow-up, 87 new cases of hyperuricemia were diagnosed. Multiple logistic regression analysis identified the accumulation of risk alleles as a significant determinant of future development of hyperuricemia (OR = 7.94; 95% CI: 1.97-53.6). In contrast, subjects with nonsense mutation predominantly showed lower UA levels (XX/XW/WW: 1.3 ± 1.7, 3.6 ± 1.0, 5.2 ± 1.4 mg/dl; p = 9.3 × 10-82). However, these subjects showed significantly reduced renal function (β = -0.111; p < 0.001) independently of possible covariates. Conclusion: Accumulation of risk genotypes was an independent risk factor for future development of hyperuricemia. Genetically developed hypouricemia was an independent risk factor for decreased renal function.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalAmerican Journal of Nephrology
Volume32
Issue number3
DOIs
Publication statusPublished - 2010 Sep 1
Externally publishedYes

Keywords

  • ABCG2
  • Longitudinal analysis
  • Polymorphism
  • SLC2A9
  • URAT1
  • Uric acid

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Association of four genetic loci with uric acid levels and reduced renal function: The J-SHIPP Suita study'. Together they form a unique fingerprint.

  • Cite this

    Tabara, Y., Kohara, K., Kawamoto, R., Hiura, Y., Nishimura, K., Morisaki, T., Kokubo, Y., Okamura, T., Tomoike, H., Iwai, N., & Miki, T. (2010). Association of four genetic loci with uric acid levels and reduced renal function: The J-SHIPP Suita study. American Journal of Nephrology, 32(3), 279-286. https://doi.org/10.1159/000318943