The geographic distribution of the most relevant ALDH2 variant, ALDH2*504Lys, is quite dramatic being present only in East Asian populations with frequencies as high as 40% in some East Asian population samples. Flushing and discomfort, such as headache and nausea, occur in many individuals of East Asian ancestry after drinking even small amounts of ethanol; these symptoms do not occur in individuals of European ancestry after drinking equivalent, and even larger, amounts of ethanol (Wolff, 1972). That early observation led to the conclusion that alcohol metabolism is quite different between these populations. Early in 1975 the atypical form of ALDH2 isozymes was found (Samatoyannopoulos et al., 1975; Greenfield & Pietruszko, 1977; Hempel & Pietruszko, 1978) including the allele designated ALDH2*2 (ALDH2*504Lys). The difference was identified as a substitution of the Glutamic acid at codon position 504 with Lysine (hence the reference to the variant allele as ALDH2*504Lys, Ikawa et al., 1983). Position 487 of the mature protein is actually codon position 504 of the gene when the mitochondrial leader sequence is included; hence the change in this genomic era from
