The contribution of polymorphism in the alcohol dehydrogenase beta subunit to alcohol sensitivity in a Japanese population

In humans, ingested alcohol is mainly metabolized by the combination of class I alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). In Orientals, there are highly frequent polymorphisms both in the class I ADH beta subunit (ADH(2)) and in the low K-m ALDH (ALDH2). We characterized the three genotypes of ALDH2 in a Japanese population. In the present study, we evaluated the effects of the ADH(2) polymorphism in the same population (424 males and 100 females) controlling for the effects of the ALDH2 polymorphism. In the ALDH2(1)/ALDH2(2) group, the frequency of facial flushing with one glass of beer was significantly higher in the ADH(2)(1)/ADH(2)(2) and ADH(2)(2)/ADH(2)(2) genotype than in the ADH(2)(1)/ADH(2)(1) genotype. Likewise, the proportion of persons with positive results for ethanol-induced cutaneous erythema differed significantly depending on the ADH(2) genotype in both the ALDH2(1)/ALDH2(1) and ALDH2(1)/ALDH2(2) genotypes. However, drinking habits were not significantly associated with the ADH(2) genotype, suggesting that the ADH(2) genotype influences the metabolism of ethanol only in the peripheral tissues.