Since these initial findings in the early 1980s, much has been learned about the genetics of alcohol metabolism. Ethanol metabolism occurs predominantly in the liver in 2 steps: (1) oxidation to acetaldehyde catalyzed by alcohol dehydrogenases (ADHs), and (2) oxidation of acetaldehyde to acetate by ALDH. Multiple genetic variants of ADH and ALDH influence rates of alcohol metabolism and alcohol dependence.13 The mechanism through which variants of these enzymes influence risk of alcohol dependence is believed to be related to elevation of acetaldehyde levels, leading to facial flushing, nausea, and tachycardia. It is hypothesized that people with the genetic variants of ADH and ALDH leading to increased acetaldehyde levels would be less likely to drink excessively because of the discomfort of ingesting a small amount of ethanol. This behavioral aversion to alcohol with increased acetaldehyde levels is exploited by administering disulfiram, a medication that interferes with ALDH, to alcoholics. Disulfiram blocks ALDH, leading to a build-up of acetaldehyde, causing symptoms including nausea, vomiting, flushing, shortness of breath, and headache when alcohol is ingested. It is hoped that the administration of disulfiram to alcoholics decreases cravings and discourages them from using alcohol.
