Genetic polymorphisms in alcohol metabolizing enzymes as related to sensitivity to alcohol-induced health effects.

Three hundred sixty-seven middle-aged Japanese men were analyzed for genotypes of low K(m) aldehyde dehydrogenase (ALDH2) and cytochrome P450 2E1, and for the association with alcohol-induced health effects. Homozygotes for the normal ALDH2 gene (NN) and for the mutant gene (MM) and heterozygotes (NM) were found in 60, 6 and 33%, and homozygotes for the c1 gene (c1/1) and c2 gene (c2/2) of P450 2E1, and heterozygotes (c1/2) in 55, 5 and 40% of subjects, respectively. Mean alcohol consumption significantly differed in the three ALDH2 genotypes: 297 g per week in NN, 158 g in NM and 18 g in MM. It was not different in the three P450 2E1 genotypes, but tended to increase from cl/1 to c2/2 in the NN subjects while there was an inverse relationship in the subjects having the M gene. No difference in alcohol-induced health effects was observed in ALDH2 genotypes, but c2/2 genotype showed higher blood pressure and serum uric acid than the other P450 2E1 genotypes in the subjects consuming 200 g or more of alcohol per week. These results suggest an interactive effect of ALDH2 and P450 2E1 genes on alcohol consumption and a higher sensitivity to alcohol-induced health effects in c2/2 genotypes, although larger scale studies are required to confirm these findings.