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 level s scarcely increased in the subjects homozygous for ALDH2()1, regardl ess 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 mu M on average, and no significant d ifferences were observed between the three ADH2 genotype groups. Subje cts homozygous for ALDH2()2 showed very high levels of blood acetalde hyde, and the average value was 79.3 mu M. The values of Widmark's bet a(60), (mg/ml/hr) and ethanol elimination rate (mg/kg/hr) showed signi ficant differences among the three ALDH2 genotypes, and in decreasing order the values were ALDH2()1/(*)1, ALDH2(*)1/(*)2, ALDH2(*)2/(*)2. However, no significant differences were seen among the ADH2 genotypes .