Genetic Association between Aldehyde Dehydrogenase 2 (ALDH2) Variation and High-Density Lipoprotein Cholesterol (HDL-C) Among Non-Drinkers in Two Large Population Samples in Japan

Abstract

Aim:Moderate alcohol consumption appears to confer some protection against coronary heart disease, which is related to an increase in high-density lipoprotein cholesterol (HDL-C). The genotype of aldehyde dehydrogenase 2 (ALDH2) is closely related to alcohol metabolism but a relationship between ALDH2 genotypes and HDL-C levels has not been proven. We undertook a large-scale correlation study between HDL-C levels and ALDH2 genotype among Japanese non-drinkers to investigate the possibility that HDL-C levels could be associated with ALDH2 genotype. Methods: We examined a population-based sample of Japanese subjects who do not consume alcohol (n 1,736) to investigate the relationship between ALDH2 genotypes and lipid or lipoprotein concentrations in serum. We also investigated whether an association between ALDH2 genotype and HDL-C levels might be found in another Japanese sample. Results:In an independent population of non-drinkers from a different geographical region of Japan, HDL-C levels were associated with the same ALDH2 genotypes. Conclusions:The results of the present study suggested that genetic variation in the ALDH2 gene can influence HDL-C levels, independent of alcohol consumption. J Atheroscler

Confirmation of ALDH2 as a Major Locus of Drinking Behavior and of Its Variants Regulating Multiple Metabolic Phenotypes in a Japanese Population

“…Since female drinkers tend to have a moderate amount of alcohol consumption (Figure S1), the observed sexual dimorphism could be explained by a dosedependent interaction between ALDH2 rs671 and HDL-C concentrations. Another Japanese study 33 reported the association between ALDH2 504Lys and low HDL-C concentrations among non-drinkers; while there was the same direction of association (β=-1.36 mg/dl, AG vs. GG), the estimated effects of ALDH2 rs671 genotype for HDL-C concentrations did not reach a nominal significance level in the present study ( Table 2 and Table S6). In contrast to HDL-C levels, LDL-C levels were significantly decreased among drinkers as compared to non-drinkers in the general population panel, in accordance with the previous report in the Japanese.…”

Aldehyde dehydrogenase 2 (ALDH2) polymorphism gene and coronary artery disease risk: a meta-analysis

“…A genetic variant that decreases ALDH2 activity, the ALDH2 polymorphism, is transmitted in an autosomal additive manner and is common in the Asian population. Wada et al (2008) found no variants of rs671 in a Caucasian population.…”

“…The mechanisms underlying this association have not been fully clarified, but may be explained based on the following reasons. First, the A allele was previously reported to be associated with lower serum high-density lipoprotein-C levels independently of alcohol consumption in Japanese subjects (Wada et al, 2008), so the ALDH2 rs671 polymorphism may influence the risk of CAD at least in part through its effects on serum high-density lipoprotein-C levels. Moreover, the ALDH2 rs671 polymorphism may increase the risk of CAD by increasing intracellular asymmetric dimethylarginine levels (Guo et al, 2010).…”

“…After reading the titles and abstracts, 65 studies were excluded because they did not exmaine CAD risk and the ALDH2 gene. The full-texts of the remaining 17 articles were reviewed (Takagi et al, 2002;Xue et al, 2007;Jo et al, 2007;Li, 2008;Wada et al, 2008;Chao, 2009;Yuan, 2009Yuan, , 2010Guo et al, 2010;Hao et al, 2010;Yijie, 2010;Yuguo, 2010;Xu et al, 2007Xu et al, , 2010Xu et al, , 2011Kotani et al, 2012;Ping, 2012). Next, an additional 6 articles were excluded [2 were repeated or overlapping studies (Li, 2008;Yuan, 2009), 2 were not case-control studies (Ji, 2008;Li, 2012); and 2 did not include the full-text (Wada et al, 2008;Kotani et al, 2012)].…”

Association of a functional single-nucleotide polymorphism in the ALDH2 gene with essential hypertension depends on drinking behavior in a Chinese Han population

“…In addition, Japanese women carrying the ALDH2 G/G homozygous genotype displayed reduced serum levels of lipid peroxides even after adjustment for alcohol intake. 25 Guo et al 26 evaluated HDL-C levels in nondrinking subjects of Chinese Han origin, and found that the homozygous rs671 A/A genotype was associated with significantly lower HDL-C concentrations compared with G/G homozygotes.…”