INVOLVEMENT OF GENETIC POLYMORPHISM OF ALCOHOL AND ALDEHYDE DEHYDROGENASES IN INDIVIDUAL VARIATION OF ALCOHOL METABOLISM

The involvement of genetic polymorphism at the alcohol dehydrogenase 2 ( ADH2 ) and aldehyde dehydrogenase 2 ( ALDH2 ) loci in determining blood acetaldehyde levels and the rate of ethanol elimination after ethanol intake was investigated. Sixty-eight healthy subjects ingested 0.4 g of ethanol per kg of body weight over 10 min. Blood acetaldehyde levels scarcely increased in the subjects homozygous for ALDH2*I , regardless of their ADH2 genotypes ( ADH2*1/*1 , ADH2*1/*2 and ADH2*2/*2 ). The acetaldehyde levels in the subjects with the ALDH2*1/*2 heterozygote increased to 23.4 μM on average, and no significant differences were observed between the three ADH2 genotype groups. Subjects homozygous for ALDH2*2 showed very high levels of blood acetaldehyde, and the average value was 79.3 μM. The values of Widmark's β60(mg/ml/hr) and ethanol elimination rate (mg/kg/br) showed significant differences among the three ALDH2 genotypes, and in decreasing order the values were ALDH2*1/*1 , ALDH2*1/*2 , ALDH2*2 However , no significant differences were seen among the ADH2 genotypes.