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Am J Nephrol. 2010;32(3):279-86. doi: 10.1159/000318943. Epub 2010 Aug 13.

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

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1
Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Ehime, Japan. tabara @ m.ehime-u.ac.jp

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.

PMID:
20714133
DOI:
10.1159/000318943
[Indexed for MEDLINE]
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