Human liver alcohol dehydrogenase: ADH_Indianapolis results from genetic polymorphism at the ADH ₂ gene locus

Abstract

New molecular forms of human liver alcohol dehydrogenase (ADH), collectively designated ADH_Indianapolis (ADH_Ind), were recently discovered in 29% of liver specimens from Black Americans [Bosron, W. F., Li, T.-K., and Vallee, B. L. (1981). Proc. Natl. Acad. Sci. USA 77:5784]. Three different ADH_Ind phenotypes have now been identified by starch gel electrophoresis, and four ADH_Ind enzyme forms isolated by affinity and ion-exchange chromatography. The most cathodic ADH_Ind form has a single pH optimum at 7.0 for ethanol oxidation and is a homodimer of a newly discovered subunit, as evidenced by dissociation-recombination studies. The remaining three purified ADH_Ind forms have dual pH optima for ethanol oxidation at 7.0 and 10.0 and generate two new bands on starch gel electrophoresis after dissociation-recombination. They appear to be heterodimers of this new subunit with the known subunits, α, β₁, and γ₁. Based on the occurrence of these four ADH_Ind isozymes and isozymes containing β₁ subunits in the homogenate supernatants of 135 livers, we conclude that ADH_Ind results from polymorphism at the ADH ₂locus, with the variant ADH ^Ind₂ allele coding for the β_Ind subunit. The frequency of ADH ^Ind₂ was 0.16 in Black Americans, and this allele was not observed in any of the 63 livers from White Americans. The frequency of the ADH ¹₃ and ADH ²₃ alleles also differed in these two populations.