Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism

The alcohol-flush reaction occurs in Asians who inherit the mutantALDH2*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 dehydrogenaseADH2 andALDH2 genotypes were determined. We also correlatedADH2, ADH3, andALDH2 genotypes with drinking behavior in 100 Chinese men. We discovered thatADH2*2 andADH3*1, alleles that encode the high activity forms of alcohol dehydrogenase, as well as the mutantALDH2*2 allele were less frequent in alcoholics than in controls. The presence ofALDH2*2 was associated with slower alcohol metabolism and the most intense flushing. In those homozygous forALDH2*1, the presence of twoADH2*2 alleles correlated with slightly faster alcohol metabolism and more intense flushing, although a great deal of variability in the latter was noted.