Alcohol dehydrogenases catalyze the first step in the oxidative metabolism of ethanol (beverage alcohol). The Arg48His coding SNP (rs1229984) in ADH1B, encoding the β subunit of alcohol dehydrogenase, dramatically affects enzyme activity; enzymes with His48 oxidize ethanol approximately 70- to 80-fold faster than those with Arg481. In East Asian populations, the His48 allele is common and lowers the risk for alcoholism, with an odds ratio of approximately 0.2 for a single allele1–4. Although it does not trigger a full flushing reaction, the protective mechanism is hypothesized to involve the aversive effects of transiently elevated acetaldehyde, conceptually similar to the protection accorded by the severe flushing experienced by individuals with the inactive variant of aldehyde dehydrogenase 2 (ALDH2)1.
