Background: Ample evidence exists for a protective effect of moderate alcohol consumption on cardiovascular risk. Recently, genotype of alcohol dehydrogenase 1C (ADH1C) has been reported to modify the impact of alcohol consumption on the risk of coronary heart disease (CHD). This study investigates whether ADH1C genotype modifies the effect of alcohol consumption on CHD risk and high-density lipoprotein (HDL) cholesterol level.
Design: Prospective cohort study.
Methods: Analyses of the joint effects of alcohol consumption and ADH1C genotype on CHD risk and HDL cholesterol level using Cox proportional hazards models and linear models.
Results: Participants who were homozygous or heterozygous for the slow metabolizing gamma2-allele and reported alcohol intake of more than 14 g/day showed a 64% [hazard rate ratio (HRR), 0.36; 95% confidence interval (CI), 0.16-0.80] reduction in CHD risk. This effect was particularly pronounced in men (HRR, 0.27; 95% CI, 0.11-0.67). Women who reported alcohol intake > or =2 g/day showed a nonsignificant risk reduction (HRR, 0.39; 95% CI, 0.07-2.17). No significant interactions were found among alcohol consumption, ADH1C genotype, and HDL cholesterol levels.
Conclusions: In this study, alcohol dehydrogenase modifies the effect of alcohol consumption on coronary risk. The results support the protective effect of alcohol consumption on CHD risk and suggest a causal association of alcohol intake and lower CHD risk. The impact of ADH1C on the relationship between alcohol and HDL cholesterol is less clear.