The genes that have been associated with alcohol dependence most consistently are those encoding the enzymes that metabolize alcohol (chemically known as ethanol). The main pathway of alcohol metabolism involves two steps. In the first step, ethanol is converted into the toxic intermediate acetaldehyde; this step is mediated by the alcohol dehydrogenase (ADH) enzymes. In a second step, the acetaldehyde is further broken down into acetate and water by the actions of aldehyde dehydrogenase (ALDH) enzymes. The genes that encode the ADH and ALDH enzymes exist in several variants (i.e., alleles) that are characterized by variations (i.e., polymorphisms) in the sequence of the DNA building blocks. One important group of ADH enzymes are the ADH class I isozymes ADH1A, ADH1B, and ADH1C. For both the genes encoding ADH1B and those encoding ADH1C, several alleles resulting in altered proteins have been identified, and the proteins encoded by some of these alleles exhibit particularly high enzymatic activity in laboratory experiments (i.e., in vitro) (Edenberg 2007). This suggests that in people carrying these alleles, ethanol is more rapidly converted to acetaldehyde.4 Several studies
