Alcohol consumption has an important effect on coronary atherosclerotic heart disease (CAD). Acetaldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism. A G-to-A missense mutation of ALDH2 gene, which causes a Glu > Lys(504) substitution, was recently shown to be associated with carotid atherosclerosis; however, its relationship with coronary atherosclerosis has not been well studied. We, therefore, investigated this relationship in Han Chinese. There are two ALDH2 alleles (1 and 2) and their combination: 1/1 (GG, typical homozygote), 1/2 (GA, heterozygote) and 2/2 (AA, atypical homozygote) in the population. Successive Han Chinese, including 89 with myocardial infarction (MI) and 142 with unstable angina, were recruited, and underwent coronary angiography and gene sequencing. Coronary atherosclerosis severity was expressed by the number of lesioned coronary arteries (>or=50% diameter stenosis) and Gensini score, calculated based on the luminal narrowing degree and its geographic importance, as assessed by angiography. Based on their ALDH2 genotypes, the 231 patients were divided into wild-type (1/1, n = 145) and mutation groups (1/2 and 2/2, n = 86). There were no significant differences in basic clinical data between the two groups; however, the mutation group had significantly higher rates of diabetes mellitus and MI, and lower prevalence of alcohol consumption than wild-type group. Yet, the two groups were not significantly different in coronary atherosclerosis severity. Multiple regression analysis has shown that the ALDH2 genotype 1/2 or 2/2 is an independent risk factor for MI, but is not associated with coronary atherosclerosis severity in Han Chinese.