The association between genotypes of urate transporter-1, serum uric acid, and mortality in the community-based population: the Yamagata (Takahata) Study.
The association between genotypes of urate transporter-1, serum uric acid, and mortality in the community-based population: the Yamagata (Takahata) Study.
复制标题
尿酸转运蛋白 1 基因型、血清尿酸和社区人群死亡率之间的关联：山形（高畑）研究。
DOI：
10.1007/s10157-019-01781-y
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
et al.
中科院分区：
文献类型：
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作者：
Kon S;Kayama T;et al.
尿酸转运蛋白-1 （URAT1）通过肾小管对尿酸的重吸收在高尿酸血症中起着至关重要的作用，其功能受编码URAT1的SLC22A12基因中几个单核苷酸多态性（snp）的调控。本研究探讨了URAT1的遗传易感性是否与一般人群的死亡率相关。方法本研究在日本高田市当地健康体检登记的1596名参与者（男性45%，平均年龄61岁），检测SLC22A12基因rs505802基因型与7年死亡率的关系。结果rs505802 GG和AG + AA基因型患者血清尿酸基线水平（平均值±SD）分别为5.1±1.3 mg/dL和5.0±1.5 mg/dL。Kaplan-Meier分析显示，GG基因型患者的死亡率显著高于AG + AA基因型患者（P= 0.09）。Cox比例风险模型校正了年龄、性别、肾功能、合并症和其他可能的混杂因素，结果显示GG基因型与死亡率显著相关[风险比（HR） 2.23, 95%可信区间（CI） 1.05 ~ 4.85, （vs. AG + AA基因型）]。此外，调整血清尿酸水平，以及上述混杂因素保持显著相关性（HR 2.26, 95% CI 1.05-4.85）。结论在日本社区人群中，URAT1遗传易感性与死亡率独立相关。这种关联可能是由于与血清尿酸水平无关的机制。
BackgroundThe 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.MethodsThis 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.ResultsThe 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).ConclusionsThis 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.