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 “487” to “504” as the referent position. As this atypical form of the enzyme was seen only in East Asians, it was also referred to as the oriental variant (Yoshida et al., 1984), the variant allele acts as a dominant negative with the heterozygote having greatly reduced enzyme activity and the homozygote having no activity; in both cases acetaldehyde accumulates as ethanol is converted to acetaldehyde. The greatly reduced enzyme activity in the heterozygous state reflects the fact that the ALDH2 tetramer is essentially a dimer of a pair of subunits with an important functional interface. If that pair is a heterodimer for the 504 Glutamate and Lysine monomers, there is essentially no activity (Larson et al., 2005).
