The association between genotypes of urate transporter-1, Serum uric acid, and mortality in the community-based population: the Yamagata (Takahata) Study
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The urate transporter-1 (URAT1) is crucial in developing hyperuricemia via reabsorption of uric acid in renal tubules, and its function is regulated by several single nucleotide polymorphisms (SNPs) within SLC22A12 gene encoding URAT1. This study investigated whether the genetic predisposition of URAT1 is associated with the mortality in general population.
This study enrolled 1596 participants (male 45%, mean age 61 years) who registered at local health checkup in Takahata, Japan, and the association between the rs505802 genotypes in SLC22A12 gene and the 7-year mortality, was examined.
The serum uric acid levels (mean ± SD) at baseline in the subjects with GG and AG + AA genotypes of rs505802 were 5.1 ± 1.3 mg/dL and 5.0 ± 1.5 mg/dL, respectively. Kaplan–Meier analysis revealed that the mortality was nonsignificantly higher in the subjects with GG genotype than in those with AG + AA genotype (P = 0.09). Cox proportional hazard model adjusted with age, gender, renal function, comorbidities, and other possible confounders, demonstrated that the GG genotype was significantly associated with the mortality [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.05–4.85, (vs. AG + AA genotype)]. Furthermore, adjustment with serum uric acid levels, along with aforementioned confounders retained the significant association (HR 2.26, 95% CI 1.05–4.85).
This study revealed that the genetic predisposition of URAT1 was independently associated with mortality in the Japanese community-based population. This association might be due to the mechanism independent of serum uric acid levels.
KeywordsUric acid Mortality SLC22A12 Snps URAT1
This study was supported in part by a Grant in-Aid from the 21st Century Center of Excellence (COE), Global COE program of the Japan Society for the Promotion of Science, a research grant of the Gout Foundation, Pfizer Inc. and Novartis Research Grants.
Compliance with ethical standards
Conflict of interest
Disclosure of potential conflicts of interest: Honoraria: Konta T (Bayer), Grants received: Konta T (Novartis, Pfizer Inc.).
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number: Yamagata University, 2006–1) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from all individual participants included in the study.
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