The polymorphism rs671 at ALDH2 associated with serum uric acid levels in Chinese Han males: A genome-wide association study.

Abstract

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 × 10-10) in the merged data. In addition, we also replicated the signal from rs3733590 at SLC2A9 (P = 1.0 × 10-10). 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 × 10-4). 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.

• Authors: Dandan Zhang, Min Yang, Dan Zhou, Zhenli Li, Libin Cai, Yuqian Bao, Hong Li, Zhongyan Shan, Juan Liu, Duo Lv, Yi Liu, Chunxiao Xu, Jie Ling, Yuyang Xu, Shuai Zhang, Qiong Huang, Yongyong Shi, Yimin Zhu, Maode Lai
• Journal: Gene (Gene) Vol. 651 Pg. 62-69 (Apr 20 2018) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 29408531 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Uric Acid
• ALDH2 protein, human
• Aldehyde Dehydrogenase, Mitochondrial

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Aldehyde Dehydrogenase, Mitochondrial (genetics)
• Asian People (genetics)
• Cohort Studies
• Female
• Genome-Wide Association Study
• Humans
• Male
• Middle Aged
• Mutation, Missense
• Polymorphism, Single Nucleotide
• Sex Factors
• Uric Acid (blood)
• Young Adult