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*1, 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 microM 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 microM. The values of Widmark's beta 60 (mg/ml/hr) and ethanol elimination rate (mg/kg/hr) showed significant 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.