ADH and ALDH genotypes in relation to alcohol metabolic rate and sensitivity.

Variation in alcohol-metabolising enzymes has been proposed as an explanation for variation in alcohol use and the effects of alcohol, and the elucidation of the effects of ALDH deficiency in Asians has reinforced this view. This paper examines evidence on the relevance of ALDH and ADH variation in people of European descent, in relation to reactions to alcohol which affect alcohol use and to variation in alcohol pharmacokinetics. Genetic variation in ALDH does not explain subjects' self-reported reactions to alcohol. The known genetic variation in ADH2 has a significant effect on blood alcohol concentrations after a standard dose of ethanol but this occurs through an effect on the peak level rather than the rate of metabolism, and the ADH3 polymorphism has no effect. The substantial genetic variation in alcohol pharmacokinetics must be due to other genes, and strategies to locate and identify them are becoming available.