Associations of ALDH2 and ADH1B genotypes with response to alcohol in Asian Americans

Objective: Individuals with alcohol dependence are less likely to possess variant alleles of the alcohol-metabolizing genes, aldehyde dehydrogenase (ALDH2*2) and alcohol dehydrogenase (ADHIB*2), than non-alcohol-dependent controls. It is hypothesized that the mechanism through which these alleles protect against alcohol dependence is by causing elevations in acetaldehyde, which in turn cause an increased response to alcohol. Previous research has shown that individuals with ALDH2*2 demonstrate enhanced reactions to alcohol compared with those without this genetic variant, but evidence that ADHIB*2 is associated with a greater alcohol response is mixed. This study was designed to determine whether the ADHIB genotype is associated with more intense reactions to alcohol after controlling for the ALDH2 genotype. Method: Participants (N = 101) were Asian American college students. Each was evaluated using objective and subjective measures before and after ingestion of alcohol and placebo beverages. Results: Participants with the ALDH2*1/*2 and ALDH2*2/*2 genotypes were more likely to experience vomiting following ingestion of the alcohol beverage than those with the ALDH2*1/*1 genotype. Participants with the ALDH2*1/*2 genotype also had greater pulse-rate increases, observed flushing ratings, and subjective feelings of intoxication 30 minutes after ingestion of alcohol than participants with the ALDH2*1/*1 genotype, despite equivalent blood alcohol concentration (BAC) measurements. Among participants with the ALDH2*1/*1 genotype, there were no additional effects of the ADHIB genotype on any measures of response to alcohol. Among participants with the ALDH2*1/*2 genotype, those with the ADHIB*2/*2 genotype were more likely to experience alcohol-induced vomiting and to report feeling less "great overall" 30 minutes after ingestion of alcohol than those with the ADHIB*1/*2 genotype. Conclusions: These findings are consistent with the hypothesis that there is an additional effect of ADHIB*2 on level of response to alcohol, but only among individuals with the ALDH2*1/*2 genotype.