Regulation of the seven human alcohol dehydrogenase genes

Abstract

The human alcohol dehydrogenase gene family consists of seven genes with distinct but overlapping patterns of expression. ADH enzymes metabolize a wide range of alcohols. Some of the ADH enzymes catalyze the first, rate-limiting step in the oxidative metabolism of ethanol. This pathway generates acetaldehyde as an intermediate, which in turn is oxidized by aldehyde dehydrogenase to acetate. Allelic differences in ADH2 and ADH3 genes encode forms of the enzymes that differ in their kinetic properties toward ethanol. These differences have been shown to affect the risk for alcoholism in Japanese and Chinese individuals (Thomasson et al. 1991; Thomasson et al. 1994; Thomasson et al. 1993; Crabb et al. 1995; Tanaka et al. 1996; Yamauchi et al. 1995; Maezawa et al. 1995; Tu and Israel, 1995). We hypothesize that differences in the expression of these genes could also affect the metabolism of ethanol, and thereby modify the risk for alcoholism in other populations.