Effect of ALDH2 Genetic Polymorphism on the Adaptive Change in Alcohol Metabolism Due to Continuous Moderate Alcohol Consumption in Humans

Abstract

Few studies have assessed the difference in adaptive changes of alcohol metabolism in the case of chronic alcohol consumption pertaining to the genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) in humans. To evaluate the influences of ALDH2 genotypes on changes in alcohol metabolism due to continuous alcohol intake, we conducted an intervention study by setting a continuous drinking period between two abstinence periods. The subjects in this study comprised 20 - 25-year-old males, including 15 males carrying ALDH2*1/*1 and 16 carrying ALDH2*1/*2 genotypes. Following the abstinence period of 4 weeks (from day 1 to day 28), all subjects drank commercially available beer (500 ml) every evening for 6 weeks (from day 30 to day 71) and subsequently abstained from drinking again for 4 weeks (from day 73 to day 100). The next morning, after the end of each period, drinking tests (DTs) were performed on each subject (DT1 on day 29, DT2 on day 72, and DT3 on day 101) to examine alcohol metabolism. The subjects drank shochu (a distilled alcoholic beverage), with an ethanol dose of 0.32 g/kg, within 20 minutes after overnight fasting. The alcohol elimination rate in subjects with ALDH2*1/*1 genotype was significantly higher during DT2 after the drinking period as compared with those at both DT1 and DT3 after the abstinence periods, whereas the elimination rate in subjects with ALDH2*1/*2 genotype did not change significantly during 3 DTs. However, blood acetaldehyde levels significantly decreased in subjects with both ALDH2 genotypes during DT2 as compared with those during DT1. The physiological subjective responses to alcohol also significantly decreased during DT2 in subjects with ALDH2*1/*2 genotype. Moreover, serum lipids, gamma-glutamyltransferase (GGT), and uric acid concentrations also varied between subjects with different ALDH2 genotypes due to continuous drinking. These results suggested that ALDH2 polymorphism modified adaptive changes in alcohol metabolism and physiological responses to continuous moderate alcohol consumption.