Alcohol metabolism in Asian-American men with genetic polymorphisms of aldehyde dehydrogenase

Background: About half of certain Asians have a deficiency of the low-K-m aldehyde dehydrogenase (ALDH2) isoenzyme. This deficiency results from inheritance of a mutant ALDH2*2 allele. Objective: To determine whether Asian Americans with ALDH2*2 alleles differ from Asian Americans without this mutation in terms of blood levels of alcohol and acetaldehyde after ingestion of a moderate amount of alcohol. Design: Double-blind, crossover study. Setting: Private research institute. Participants: 35 healthy Asian-American men. Three men who became ill after alcohol ingestion and one who had outlying data were excluded. Intervention: Alcoholic beverage, containing 0.56 g of alcohol per kg of body weight, or placebo beverage, containing 3 mL of alcohol, given orally on separate occasions. Measurements: Blood levels of alcohol and acetaldehyde measured before and several times after ingestion of the alcoholic or placebo beverage. Results: Participants with ALDH2*2 alleles had significantly higher blood acetaldehyde levels after ingesting alcoholic and placebo beverages than did participants with ALDH2*1 alleles, despite similar blood alcohol concentrations. Conclusions: Blood acetaldehyde levels rather than blood alcohol concentration may mediate enhanced alcohol sensitivity among Asians with ALDH2*2 alleles.