In addition to the pharmacodynamic effects reviewed above, another source of genetic influence on the subjective effects of alcohol comes from genetically-mediated differences in the metabolism of alcohol as it travels through the body, or in other words, alcohol’s pharmacokinetics. When alcohol is consumed, its metabolic breakdown is a three-step hepatic process in which the alcohol is first oxidized into acetaldehyde by the enzyme alcohol dehydrogenase (ADH) and is then further metabolized into acetate, and other byproducts, by the enzyme aldehyde dehydrogenase (ALDH). The genes responsible for these enzymes exert important influences on the subjective effects of alcohol because they determine the relative levels of these metabolites over the course of alcohol metabolism. Indeed, genes underlying the pharmacokinetics of alcohol are among the best characterized in terms of their influence on subjective responses to alcohol and alcoholism risk.
