LOW-FREQUENCY OF THE ADH2(ASTERISK)2 ALLELE AMONG ATAYAL NATIVES OF TAIWAN WITH ALCOHOL-USE DISORDERS

Genetic variation at two polymorphic alcohol dehydrogenase loci, ADH2 and ADH3 and at the polymorphic mitochondrial aldehyde dehydrogenase l ocus, ALDH2, may influence the risk of developing alcoholism by modula ting the rate of elimination of ethanol and the rate of formation and elimination of acetaldehyde. Populations differ in allele frequencies at these loci. We determined the genotypes at all three of these loci in Atayal natives of Taiwan. The frequencies of ADH22, ADH3*1, and AL DH21 alleles (0.91, 0.99, and 0.95, respectively) were significantly higher among the Atayal than among a predominantly Han Chinese populat ion from Taiwan. Among the Atayal, the group with alcohol use disorder s (alcohol dependence and alcohol abuse) had a significantly lower fre quency of the ADH22 allele (0.82) than those without alcohol use diso rders (0.91). The ADH22 allele encodes the beta(2) subunit; isozymes containing 82 subunits oxidize alcohol faster in vitro than the beta(1 ) beta(1) isozyme encoded by ADH21. Thus, the simplest explanation fo r these data is that individuals with a beta(2) isozymes have a higher rate of ethanol oxidation, which is a deterrent to alcohol abuse and dependence in some individuals. The Atayal with alcohol use disorders also had a lower frequency of ALDH22 than the controls; this allele i s known to be responsible for the alcohol-flush reaction among Asians, and thereby deters drinking.