An examination of ALDH2 genotypes, alcohol metabolism and the flushing response in Native Americans

OBJECTIVE: The study was designed to examine the relationship between aldehyde dehydrogenase (ALDH2) genotype and the flushing response in a population of Native Americans. METHOD: Objective measures of the flushing response were obtained by monitoring skin temperature, heart rate, blood pressure, as well as blood alcohol concentrations, in flushing and nonflushing Native Americans (n = 105) as well as in Oriental (n = 15) and white (n = 15) control subjects following a dose of alcohol (0.2 or 0.4 gm/kg). ALDH genotypes were determined via polymerase chain reaction followed by hybridization to 32P or biotin-labeled allele-specific oligonucleotide probes. RESULTS: There were no ALDH2 mutations detectable in Native Americans reporting the flushing response, nor any objective evidence of an Oriental-like response to alcohol. The rate of alcohol metabolism was shown to be the same among whites, Native flushers and Native nonflushers. CONCLUSIONS: The results demonstrate that the flushing reaction experienced by Native Americans appears to be milder and less unpleasant than the "Oriental" flushing reaction, with little effect on drinking frequency and amount. In addition, the flushing is not mediated by the ALDH2 mutation or elevated blood acetaldehyde. A critical analysis of the discrepancies in the literature regarding alcohol metabolism in Native Americans is provided.