Influence of ADH and ALDH2 on clinical features of alcohol dependence

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase-2 (ALDH2) play central roles in the metabolism of ethanol and its metabolite, acetaldehyde, in the liver. Genes encoding these enzymes show polymorphisms capable of altering metabolic activities. We have examined the relationship between genetic variations of these enzymes and alcohol-related disorders in Japanese. The results revealed that the less active allele of the ADH2 gene (ADH2*1) is associated with an increased risk for alcohol dependence, alcohol-induced persistent amnestic disorder, and cancers of the upper gastrointestinal (GI) tract, and with the severity of the acute withdrawal syndrome. On the other hand, the inactive allele of the ALDH2 gene (ALDH2*2) is associated with reduced alcohol consumption in the general Japanese population, a decreased risk for alcohol dependence, and an increased risk for the cancers in the same region. Possible mechanisms for these associations are discussed.