Zhang Dandan, Yang Min, Zhou Dan, Li Zhenli, Cai Libin, Bao Yuqian, Li Hong, Shan Zhongyan, Liu Juan, Lv Duo, Liu Yi, Xu Chunxiao, Ling Jie, Xu Yuyang, Zhang Shuai, Huang Qiong, Shi Yongyong, Zhu Yimin, Lai Maode
Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China; Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang 310058, PR China.
Department of Nutrition and Food Safety, School of Public Health, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.
Gene. 2018 Apr 20;651:62-69. doi: 10.1016/j.gene.2018.01.064. Epub 2018 Feb 7.
Serum uric acid (SUA) levels are highly heritable and an increased SUA level is one of important risk factors for gout, diabetes, metabolic syndrome, and cardiovascular diseases. The genetic variants underlying SUA remains largely unexplored. The aim was to explore new genetic variants underlying SUA in Chinese Han. We performed a genome-wide association study of SUA levels in Han Chinese. The discovery set contained 1634 samples and subsequent replication was comprised of 1649 females and 1169 males. 2620 subjects were recruited in the detailed analysis of rs671, alcohol drinking and SUA. We found a genome-wide significant association between SUA level and the SNP rs671 at ALDH2 (P = 1.2 × 10) in the merged data. In addition, we also replicated the signal from rs3733590 at SLC2A9 (P = 1.0 × 10). In males, about 0.21% to 1.95% of the total variance for SUA can be explained by rs671 using linear regression models in four independent cohorts. Of those, 56.75% to 93.51% might be explained by altering alcohol consumption due to rs671. No statistical association of rs671 and SUA was observed in females (P = 0.409). Furthermore, we observed a causal relationship between alcohol consumption and SUA in males using rs671 as an instrumental variable (P = 5.1 × 10). We replicated the previous findings in SLC2A9. Our evidence supported that rs671 was associated with SUA by affecting alcohol consumption in males. This finding strongly suggests a role for alcohol consumption in the development of hyperuricaemia and uric acid related traits.
血清尿酸（SUA）水平具有高度遗传性，SUA水平升高是痛风、糖尿病、代谢综合征和心血管疾病的重要危险因素之一。SUA潜在的基因变异在很大程度上仍未被探索。目的是探索中国汉族人群中SUA潜在的新基因变异。我们对汉族人群的SUA水平进行了全基因组关联研究。发现集包含1634个样本，随后的复制样本包括1649名女性和1169名男性。在对rs671、饮酒与SUA的详细分析中招募了2620名受试者。我们在合并数据中发现SUA水平与ALDH2基因的SNP rs671之间存在全基因组显著关联（P = 1.2×10）。此外，我们还重复验证了SLC2A9基因rs3733590位点的信号（P = 1.0×10）。在男性中，使用线性回归模型，在四个独立队列中，rs671可解释SUA总变异的约0.21%至1.95%。其中，56.75%至93.51%可能是由于rs671改变饮酒量所致。在女性中未观察到rs671与SUA的统计学关联（P = 0.409）。此外，我们使用rs671作为工具变量观察到男性饮酒与SUA之间存在因果关系（P = 5.1×10）。我们重复验证了先前在SLC2A9中的发现。我们的证据支持rs671通过影响男性饮酒与SUA相关。这一发现强烈表明饮酒在高尿酸血症及尿酸相关性状的发生发展中起作用。
