It is likely that the ALDH1A1 and ALDH1B1 enzymes significantly contribute to acetaldehyde metabolism only in situations where ALDH2 is inactivated, either pharmacologically or because of the presence of the ALDH2*2 allele. The KM values3 of the ALDH1A1 and ALDH1B1 enzymes exceed those of the ALDH2 enzyme by at least 100-fold, and, thus, are not likely to be operating at full capacity when acetaldehyde levels are kept at the usual physiological state (i.e., below 5 μmol/L) (Klyosov et al. 1996; Stagos et al. 2010). Numerous polymorphisms have been identified for the ALDH1A1 gene, and linkage to alcohol-related phenotypes has been found in both European populations (rs8187974 [Lind et al. 2008; Sherva et al. 2009]) and people of Indo-Trinidadian background (ALDH1A1*2, rs67952887 [Moore et al. 2007]). In addition, a functional polymorphism (i.e., rs2228093) in the ALDH1B1 gene found in northern European populations seems to correlate with alcohol-aversive reactions (Husemoen et al. 2008; Linneberg et al. 2010), suggesting that the ALDH1A1 and ALDH1B1 isoenzymes contribute to ethanol metabolism under typical ethanol loads even in populations where the ALDH2*2 allele virtually is nonexistent.
