The genes with the clearest contribution to the risk for alcoholism and alcohol consumption are alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2; mitochondrial aldehyde dehydrogenase), two genes central to the metabolism of alcohol (Figure 1)20. Alcohol is metabolized primarily in the liver, although there is some metabolism in the upper GI tract and stomach. The first step in ethanol metabolism is oxidation to acetaldehyde, catalyzed primarily by ADHs; there are 7 closely related ADHs clustered on chromosome 4 (reviewed in20). The second step is metabolism of the acetaldehyde to acetate by ALDHs; again, there are many aldehyde dehydrogenases, among which ALDH2 has the largest impact on alcohol consumption20.
