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
Externally publishedYes

Fingerprint

Hyperuricemia
Genetic Loci
Uric Acid
Nonsense Codon
Kidney
Genetic Crosses
Genotype
Personal Health Records
Genome-Wide Association Study
Serum
Logistic Models
Alleles
Regression Analysis
Population

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Tabara, Y., Kohara, K., Kawamoto, R., Hiura, Y., Nishimura, K., Morisaki, T., ... 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

Association of four genetic loci with uric acid levels and reduced renal function : The J-SHIPP Suita study. / Tabara, Yasuharu; Kohara, Katsuhiko; Kawamoto, Ryuichi; Hiura, Yumiko; Nishimura, Kunihiro; Morisaki, Takayuki; Kokubo, Yoshihiro; Okamura, Tomonori; Tomoike, Hitonobu; Iwai, Naoharu; Miki, Tetsuro.

In: American Journal of Nephrology, Vol. 32, No. 3, 09.2010, p. 279-286.

Research output: Contribution to journalArticle

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, vol. 32, no. 3, pp. 279-286. https://doi.org/10.1159/000318943
Tabara, Yasuharu ; Kohara, Katsuhiko ; Kawamoto, Ryuichi ; Hiura, Yumiko ; Nishimura, Kunihiro ; Morisaki, Takayuki ; Kokubo, Yoshihiro ; Okamura, Tomonori ; Tomoike, Hitonobu ; Iwai, Naoharu ; Miki, Tetsuro. / Association of four genetic loci with uric acid levels and reduced renal function : The J-SHIPP Suita study. In: American Journal of Nephrology. 2010 ; Vol. 32, No. 3. pp. 279-286.
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