The higher ADH enzyme activity encoded by the polymorphisms ADH1B*2 (Arg48His, rs1229984), ADH1B*3 (Arg370Cys, rs2066702), and the ADH1C*1 haplotype (Arg272Ile350) enables more rapid conversion of ethanol to acetaldehyde, thereby also resulting in the flushing syndrome and also being protective against excessive alcohol consumption. The ADH1B*2 allele, occurring at a frequency of 0.75 in East Asians, is uncommon in AI with a frequency of ≤ 0.01.43 The ADH1B*3 allele, occurring at a frequency of 0.04 in Southwest California Indians, has been associated with a protective effect on risk for alcoholism in this population.42,44 In summary, studies to date in AI/AN individuals have shown that variation in genes encoding ethanol metabolizing enzymes has little if any impact on risk for AUD.
