Evaluation of the use of self-reported facial flushing and ethanol patch test for ALDH2 genotypes

It is generally assumed that subjects with ALDH2*1/1 do not exhibit flushing symptoms after alcohol intake, but recent studies have revealed discordance in ALDH2 genotypes with self-reported facial flushing and the ethanol patch test. We evaluated the reliability of a facial flushing questionnaire and the ethanol patch test in 495 Japanese volunteers. Genomic DNA was extracted from peripheral blood samples and amplified by polymerase chain reaction (PCR) to detect ALDH2 polymorphisms as reported previously. The subjects were classified by the presence or absence of facial flushing using a questionnaire. Ethanol patch tests were performed using the previously described method. Each subject's alcohol consumption was established through a questionnaire. In each gender, there was a high frequency of facial flushing and positive ethanol patch tests in ALDH2*1/1 subjects. Alcohol consumption was not significantly different between ALDH2*1/1 subjects with positive and negative results. However, alcohol consumption in the positive ALDH2*1/1 group was significantly higher than that of ALDH2*1/2 subjects in both tests, indicating that the positive results may lead to variance with ALDH2*1/1. Most of the ALDH2*1/2 subjects exhibited facial flushing and a positive patch test. Meanwhile, 100% in the ALDH2*2/2 group exhibited positive results. There was no significant gender difference in either facial flushing or ethanol patch test reactions. In addition, the frequency of both male and female ALDH2*1/1 subjects with positive flushing and ethanol patch test reactions increased roughly in proportion to drinking frequency, but no significant differences were observed between them. Consequently, the general use of self-reported facial flushing or ethanol patch tests instead of ALDH2 genotyping should be carefully handled for genetic association studies of drinking behavior and alcohol-related diseases.