Atherosclerotic diseases are thought to be less frequent in Asians compared with Caucasians. Unlike Caucasians, nearly half of Asians have a functional deficiency in the low Km aldehyde dehydrogenase (ALDH2), a key enzyme in alcohol metabolism, which potentially modifies the prevalence of atherosclerosis. This study examined the associations between ALDH2 genotypes ("typical homo," "hetero" or "atypical homo") and carotid atherosclerosis in 304 Japanese patients. As a measure of carotid atherosclerosis, plaque score (PS) was evaluated by B-mode ultrasonography. Age- and sex-adjusted PS was lower in "atypical homo" genotype patients (2.7 +/- 1.2 [mean +/- standard error], n=21) (p<0.05) and tended to be lower in "hetero" patients (4.5 +/- 0.5, n=116) (p=0.07) compared with "typical homo" patients (5.7 +/- 0.4, n=167). When we controlled for traditional cardiovascular risk factors and alcohol intake, the "atypical homo" genotype was found to be associated with lower PS (beta=-0.13, p<0.05). Based on these findings, the ALDH2 genotypes seem to be associated with the severity of carotid atherosclerosis, potentially modifying the prevalence of atherosclerosis in Asians.