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

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 ²₂ was 0.68.