LAUSR

AIMS The potential effect of alcohol consumption on coronary heart disease (CHD) remains unclear. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in subclinical and clinical CHD. METHODS We conducted two Mendelian randomization studies: a cross-sectional study of coronary artery calcification (CAC) on computed tomography of 1029 healthy men (mean age, 63.8 years) and a case-control study of 421 men with CHD (acute coronary syndrome [ACS] or stable angina pectoris) who underwent coronary revascularization and 842 age-matched male controls. RESULTS In the CAC study, medians (25%tiles, 75%tiles) of alcohol consumption by ALDH2-rs671 *2 homozygotes (n = 86 [8.4%]), *1*2 heterozygotes (n = 397 [38.5%]), and *1 homozygotes (n = 546 [53.1%]) were 0.0 (0.0, 0.0), 28.0 (0.0, 129.0), and 224.0 (84.0, 350.0) g/week, respectively. In age-adjusted Poisson regression with robust error variance, compared with *2 homozygotes, relative risks for prevalent CAC score >0, ≥100, and ≥300 in *1 homozygotes were 1.29 (95% confidence interval, 1.06-1.57), 1.76 (1.05-2.96), and 1.81 (0.80-4.09), respectively. In age-adjusted ordinal logistic regression for CAC distributions, we observed higher odds among *1 homozygotes (odds ratio, 2.19 [1.39-3.46]) and even among *1*2 heterozygotes (1.77 [1.11-2.82]) compared with *2 homozygotes. In the case-control study, conditional logistic regression revealed lower prevalence of *1 homozygotes among men with CHD (odds ratio, 0.54 [0.35-0.82]), especially ACS (0.46 [0.27-0.77]), than controls. CONCLUSION Our findings indicate a positive association of alcohol consumption with CAC burden but an inverse association with clinical CHD, especially ACS.