Journal Article

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 Liu, Qiang Ding, Jeffrey M Trent, S. Lilly Zheng, Zengnan Mo and Jianfeng Xu

in Human Molecular Genetics

Volume 21, issue 7, pages 1658-1664
Published in print April 2012 | ISSN: 0964-6906
Published online December 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr587
A genome-wide association and gene–environment interaction study for serum triglycerides levels in a healthy Chinese male population

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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.

Journal Article.  4019 words.  Illustrated.

Subjects: Genetics and Genomics

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