A mechanistic pathway has been proposed for how possessing ALDH2*2 and ADH1B*2 alleles may reduce an individual’s risk for alcohol dependence (Eriksson, 2001; Li, 2000; Thomasson et al., 1991; see Wall, 2005). Based on their kinetic properties, ADH1B*2 should lead to faster production of acetaldehyde than ADH1B*1 (Bosron and Li, 1986) and ALDH2*2 should lead to slower elimination of acetaldehyde than ALDH2*1 (Wilken, 1981). These increased acetaldehyde levels are hypothesized to lead to heightened responses to alcohol, which in turn are predicted to discourage heavy alcohol consumption. Lower alcohol consumption is then proposed to reduce the likelihood of an individual developing an AUD. Although there is much evidence to support this mechanism for ALDH2*2, the data supporting this mechanism for ADH1B*2 has been less consistent (Eriksson, 2001; see Wall, 2005). The present study was undertaken to better understand early steps of the mechanistic pathway relating ALDH2 and ADH1B polymorphisms to lower rates of AUDs. The primary objective was to clarify associations of ALDH2 and ADH1B variations with low-dose reactions and initial sensitivity to alcohol.
