A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population

Aihua Tan, Jielin Sun, Ning Xia, Xue Qin, Yanling Hu, Shijun Zhang, Sha Tao, Yong Gao, Xiaobo Yang, Haiying Zhang, Seong Tae Kim, Tao Peng, Xiaoling Lin, Li Li, Linjian Mo, Zhengjia Liang, Deyi Shi, Zhang Huang, Xianghua Huang, Ming LiuQiang Ding, Jeffrey M. Trent, S. Lilly Zheng, Zengnan Mo, Jianfeng Xu

Research output: Contribution to journalArticlepeer-review

Abstract

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10-26 and 1.41 × 10-9 for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10-5). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10-10), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10-8 for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.

Original languageEnglish (US)
Article numberddr587
Pages (from-to)1658-1664
Number of pages7
JournalHuman molecular genetics
Volume21
Issue number7
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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