Polymorphism of human liver alcohol dehydrogenase: identification of ADH2 2-1 and ADH2 2-2 phenotypes in the Japanese by isoelectric focusing.

TL;DR: An agarose isoelectric focusing procedure was developed that clearly separated the atypical Japanese livers into two groups, A1 and A2, which are the homozygous and type A2 livers, the heterozygous ADH2 2-1 phenotype.

Abstract: Liver homogenate-supernatants from most Japanese exhibit an “atypical” pH optimum for ethanol oxidation at pH 8.8 instead of 10.5, the “typical” pH-activity optimum. It has been proposed that atypical livers contain alcohol dehydrogenase isozymes with β2 subunits while typical livers contain isozymes with β1 subunits, both produced by the ADH 2 gene. Because it is difficult to differentiate the atypical ADH2 2-2 phenotype from the ADH2 2-1 phenotype by starch gel electrophoresis, an agarose isoelectric focusing procedure was developed that clearly separated the atypical Japanese livers into two groups, A1 and A2. The ββ isozymes in A1 and A2 livers were purified. Type A1 livers contained a single ββ isozyme with an atypical pH-rate profile; it was designated β2β2. Three ββ isozymes were isolated from A2 livers, two of which corresponded to β1β1 and β2β2. A third, absent from the typical and the atypical A1 livers, had an intermediate mobility; it was designated β2β1. Type A1 livers are, therefore, the homozygous ADH2 2-2 phenotype, and type A2 livers, the heterozygous ADH2 2-1 phenotype. The ADH2 2-2 phenotype was found in 53% of 194 Japanese livers, and the ADH2 2-1 phenotype, in 31%. Accordingly, the frequency of ADH 2 2 was 0.68.