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Clinical and Experimental Nephrology

, Volume 23, Issue 12, pp 1357–1363 | Cite as

The association between genotypes of urate transporter-1, Serum uric acid, and mortality in the community-based population: the Yamagata (Takahata) Study

  • Soichiro Kon
  • Tsuneo KontaEmail author
  • Kazunobu Ichikawa
  • Masafumi Watanabe
  • Hidenori Sato
  • Kenichi Ishizawa
  • Yoshiyuki Ueno
  • Hidetoshi Yamashita
  • Takamasa Kayama
Original article
  • 117 Downloads

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords

Uric acid Mortality SLC22A12 Snps URAT1 

Notes

Acknowledgements

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.

Informed consent

Written informed consent was obtained from all individual participants included in the study.

Supplementary material

10157_2019_1781_MOESM1_ESM.pptx (43 kb)
Supplementary Fig. 1. Seven years survival curve by GG/AG+AA genotype in rs505802 in SLC22A12 gene and the presence/absence of hyperuricemia (PPTX 43 kb)

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Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  1. 1.Department of Cardiology, Pulmonology and NephrologyYamagata University School of MedicineYamagataJapan
  2. 2.Department of Public Health and HygieneYamagata University Graduate School of Medical ScienceYamagataJapan
  3. 3.Global Center of ExcellenceYamagata University School of MedicineYamagataJapan

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