This is the first study to examine the relationship between alcohol metabolizing genes and retrospective reports of level of response to alcohol during the first five lifetime drinking episodes. Initial sensitivity to alcohol as measured by the SRE_5 has been prospectively associated with later alcohol consumption, dependence symptoms, and AUDs in adolescent, college student, and adult samples (Morean and Corbin, 2008; Schuckit et al. 2007; 2008). Our findings are consistent with previous research using the total SRE score that demonstrated high response to alcohol in individuals with an ALDH2*2 allele when assessed across multiple periods of drinking (Wall et al., 1999); our results further indicate the heightened response to alcohol seen in individuals with ALDH2*2 and ADH1B*2 alleles is apparent from the very onset of alcohol use (SRE_5 score) and may be indicative of an innate sensitivity rather than a rapid tolerance response. Importantly, ADH1B*2 being associated with initial lifetime responses to alcohol in ALDH2 heterozygotes offers another line of data to support ADH1B having an effect on sensitivity to alcohol, which has not been consistently reported in the literature.
