Genetically-induced variability of alcohol metabolism and its effect on drinking behavior and predisposition to alcoholism

Alcoholism is one of the most challenging current health problems in the Western countries with far-reaching medical, social, and economic consequences. There are a series of factors that interact in predisposing or protecting an individual against alcoholism and alcohol-related disorders. This article surveys the state of our knowledge concerning the biochemical and genetic variations in alcohol metabolism and their implications in alcohol sensitivity, alcohol drinking habits, and alcoholism in different racial/ethnic groups. The major pathway for the degradation of ethanol is its oxidation to hydrogen and acetaldehyde--to which many of the toxic effects of ethanol can be attributed. Variations in alcohol and acetaldehyde metabolism via genetically determined polymorphisms in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) seem to play an important role in individual and racial differences in acute and chronic reactions to alcohol, alcohol drinking habits, as well as vulnerability to organ damage after chronic alcohol abuse. Alcohol sensitivity and associated discomfort symptoms accompanying alcohol ingestion may be determinental for the significantly low incidence of alcoholism among the Japanese, Chinese and other Orientals of Mongoloid origin. An abnormal ALDH isozyme has been found to be widely prevalent among individuals of the Mongoloid race and is mainly responsible for the acute sensitivity to alcohol commonly observed in this race. Persons sensitive to alcohol by virtue of their genetically controlled ALDH isozyme deficiency may be discouraged from drinking large amounts of alcohol in their daily life due to the initial adverse reaction experienced after drinking alcohol. Indeed, a significantly low incidence of the mitochondrial ALDH isozyme deficiency has been observed in alcoholics as compared to psychiatric patients, drug dependents and healthy controls in Japan. How far any variation in ADH and/or ALDH activity among individuals of Caucasian origin will have similar effects has yet to be studied.