Independent effects of ADH1B and ALDH2 common dysfunctional variants on gout risk.
Independent effects of ADH1B and ALDH2 common dysfunctional variants on gout risk.
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DOI：
10.1038/s41598-017-02528-z
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发表时间：
2017-05-31
影响因子：
4.6
通讯作者：
Shinomiya N
中科院分区：
文献类型：
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作者：
Sakiyama M;Matsuo H;Akashi A;Shimizu S;Higashino T;Kawaguchi M;Nakayama A;Naito M;Kawai S;Nakashima H;Sakurai Y;Ichida K;Shimizu T;Ooyama H;Shinomiya N
痛风是由高尿酸血症引起的，饮酒是一个既定的危险因素。乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）是酒精代谢的关键酶。我们最近进行了一项痛风的全基因组关联研究，随后进行了一项精细定位研究，将ALDH 2的rs671确定为痛风位点。然而，痛风与ADH 1B常见变体之间的关联迄今尚未报道，这促使我们研究痛风与ADH 1B（rs 1229984）和ALDH 2（rs671）常见功能障碍变体之间的关联。我们使用了1，048例临床定义的痛风病例和1，334例日本男性对照。ADH 1B的rs 1229984（His 48 Arg）的“His携带者”（His/His或His/Arg）显著增加痛风风险（P = 4.3 × 10−4，比值比= 1.76），ALDH 2的rs671（Glu 504 Lys）的“非Lys携带者”（Glu/Glu）也是如此。此外，ADH 1B和ALDH 2的常见变体与痛风独立相关。我们的研究结果同样表明，这些变异的基因分型可以用于痛风风险的评估。
Gout is caused by hyperuricemia, with alcohol consumption being an established risk factor. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are crucial enzymes for alcohol metabolism. We recently performed a genome-wide association study of gout and a subsequent fine-mapping study which identified rs671 of ALDH2 as a gout locus. However, the association between gout and common variants of ADH1B has hitherto remained unreported, prompting us to investigate the association between gout and common dysfunctional variants of ADH1B (rs1229984) and ALDH2 (rs671). We used 1,048 clinically defined gout cases and 1,334 controls of Japanese male. The “His carrier” (His/His or His/Arg) of rs1229984 (His48Arg) of ADH1B significantly increased gout risk (P = 4.3 × 10−4, odds ratio = 1.76), as did the “non-Lys carrier (Glu/Glu)” of rs671 (Glu504Lys) of ALDH2. Furthermore, common variants of ADH1B and ALDH2 are independently associated with gout. Our findings likewise suggest that genotyping these variants can be useful for the evaluation of gout risk.