Association of polymorphism in the alcohol dehydrogenase 2 gene with alcohol-related organ injuries, especially liver cirrhosis

The class I hepatic alcohol dehydrogenases (ADHs) are primarily responsible for ethanol metabolism in humans. Genetic polymorphism at the ADH2 locus results in the inheritance of isozymes of strikingly different catalytic properties. In European and Caucasian American populations, beta 1, which is encoded by ADH2(1), is the most common form of the enzyme, while beta 2, encoded by the ADH2(2) allele, is found primarily in Orientals. The beta 2 beta 2 enzyme encoded by ADH2(2)/ADH2(2) is approximately 20 times more active in ethanol oxidation than the beta 1 beta 1 enzyme. In vivo the kinetic differences of ADH2 isozymes may influence individual risk, for the effects of ethanol. This article will review the role of polymorphisms at the ADH2 loci in genetic predisposition to alcoholism and alcohol-related organ injury, especially alcoholic cirrhosis.