Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism

Abstract

The alcohol-flush reaction occurs in Asians who inherit the mutant ALDH2*2 allele that produces an inactive aldehyde dehydrogenase enzyme. In these individuals, high blood acetaldehyde levels are believed to be the cause of the unpleasant symptoms that follow drinking. We measured the alcohol elimination rates and intensity of flushing in Chinese subjects in whom the alcohol dehydrogenase ADH2 and ALDH2 genotypes were determined. We also correlated ADH2, ADH3, and ALDH2 genotypes with drinking behavior in 100 Chinese men. We discovered that ADH2*2 and ADH3*1, alleles that encode the high activity forms of alcohol dehydrogenase, as well as the mutant ALDH2*2 allele were less frequent in alcoholics than in controls. The presence of ALDH2*2 was associated with slower alcohol metabolism and the most intense flushing. In those homozygous for ALDH2*1, the presence of two ADH2*2 alleles correlated with slightly faster alcohol metabolism and more intense flushing, although a great deal of variability in the latter was noted.