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 o f class I alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH ). In Orientals, there are highly frequent polymorphisms both in the c lass I ADH beta subunit (ADH(2)) and in the low K-m ALDH (ALDH2). We c haracterized the three genotypes of ALDH2 in a Japanese population. In the present study, we evaluated the effects of the ADH(2) polymorphis m in the same population (424 males and 100 females) controlling for t he effects of the ALDH2 polymorphism. In the ALDH2(1)/ALDH2(2) group, the frequency of facial flushing with one glass of beer was significan tly 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 AL DH2(1)/ALDH2(1) and ALDH2(1)/ALDH2(2) genotypes. However, drinking hab its were not significantly associated with the ADH(2) genotype, sugges ting that the ADH(2) genotype influences the metabolism of ethanol onl y in the peripheral tissues.