The combination of mitochondrial low enzyme-activity aldehyde dehydrogenase 2 allele and superoxide dismutase 2 genotypes increases the risk of hypertension in relation to alcohol consumption

Abstract

A cooperative role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and superoxide dismutase 2 (SOD2) to maintain the vascular function has recently been demonstrated in nitrate tolerance. The present study examined whether the combination of low enzyme-activity variants of ALDH2 and SOD2 increases the risk of hypertension in relation to alcohol consumption. A total of 444 Japanese participants in a health-screening program were evaluated. The risk of hypertension among the individuals harboring both the ALDH2*2 allele and the SOD2 Val/Val genotype was significantly higher in drinkers than in nondrinkers (adjusted odds ratio, 6.22; 95% confidence interval, 2.26-17.1; P<0.001). Among these individuals, the systolic/diastolic blood pressure also increased by 0.24/0.14 mmHg for each 1g/day increase in alcohol consumption (P<0.001/P=0.003). These associations were observed, but the degree was lower among those with the other genotype combinations (0.11/0.10 mmHg; P=0.012/P=0.001). Information about the genetic predisposition to alcohol-related diseases may thus be useful to promote lifestyle modifications for high-risk individuals.

Meta-Analysis on the Association of ALDH2 Polymorphisms and Type 2 Diabetic Mellitus, Diabetic Retinopathy

“…The acetaldehyde is a substance with high reactivity and mutagenesis. The accumulation of acetaldehyde could induce acute cardiovascular reactions, such as facial flushing, tachycardia, and orthostatic hypotension [20,26,27]. Rs671 mutation leads to ALDH2 dysfunction and results in the accumulation of aldehydes.…”

Associations between aldehyde dehydrogenase 2 (ALDH2) genetic polymorphisms, drinking status, and hypertension risk in Japanese adult male workers: a case–control study

“…According to a genome-wide association study on blood pressure in East Asians [24], one of the most prominent blood pressure associations was detected on the ALDH2 locus. Furthermore, Nakagawa et al [25] reported that alcohol intake dose-dependently increases the risk of HT and elevates SBP and DBP to a considerably greater extent in ALDH2*2 allele carriers than in noncarriers. In this study, SBP and DBP were significantly higher in participants who harbored the ALDH2 genetic polymorphism *1/*1 than in those who harbored the ALDH2 genetic polymorphism *1/*2 or *2/*2.…”

Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9

“…We analyzed all individuals but adjusted for population stratification through the genomic control method. Candidate gene studies in Japanese, Chinese, and Brazilian populations have reported gene-alcohol interactions (Kokaze et al, 2004, 2007; Pan et al, 2010; Chang et al, 2012; Chen et al, 2013; Leite et al, 2013; Nakagawa et al, 2013; Sen Zhang et al, 2013; Wang et al, 2013). Thus, by broadening the investigation of interactions between alcohol and genes to other ethnic groups, we may be able to capitalize on population-specific variants, different distributions of alcohol consumption, and different linkage disequilibrium patterns.…”

“…Yet, the effect of light-to-moderate alcohol consumption remains controversial (Klatsky and Gunderson, 2008; Leite et al, 2013) with mounting evidence that the genetic composition of an individual impacts the effect of alcohol consumption on hypertension risk. Candidate gene studies of hypertension and BP have implicated several interactions between alcohol and genes [ ADH2 (Sen Zhang et al, 2013), ALDH2 (Chang et al, 2012; Nakagawa et al, 2013; Wang et al, 2013), SOD2 (Nakagawa et al, 2013), LEPR (Sober et al, 2009), ApoE (Leite et al, 2013), CYP11B2 (Pan et al, 2010), NADH2 (Kokaze et al, 2004, 2007), GNB3 (Polonikov et al, 2011), and ADM (Chen et al, 2013)].…”