Effects of ADH1B and ALDH2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men.

Abstract

The genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol (sEtOH) levels are well correlated with blood EtOH levels. To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde (sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours. The initial sEtOH levels did not differ between the ADH1B*2 group (n=50) and the ADH1B*1/*1 group (n=49) (median: 0.617 vs. 0.762mg/ml). The salivary AER (sAER) increased as the sEtOH levels increased (p<0.0001). After stratification according to the sEtOH levels (<0.4, 0.4 to 0.99, and ≥1.00mg/ml), the median sAER of the ADH1B*2 group was 0.075, 0.188, and 0.228mg/ml/h, respectively, and that of the ADH1B*1/*1 group was 0.037, 0.115, and 0.233mg/ml/h, respectively. The sAER of the ADH1B*2 group was faster than that of the ADH1B*1/*1 group overall (p=0.001) and when the sEtOH category was 0.4 to 0.99mg/ml (p<0.0001). The ADH1B genotype and the sEtOH levels had an interaction effect on the sAER (p=0.036). A multiple linear regression analysis with a stepwise procedure selected the ADH1B*2 allele (p=0.004) and the sEtOH levels (p<0.0001) as positive predictors of sAER. The sAER did not differ according to the ALDH2 genotype. The sAcH levels were higher than the blood AcH levels reported in alcoholics, probably because of AcH production by oral microorganisms. The sAcH of the ALDH2*1/*2 group (n=18) was higher than that of the ALDH2*1/*1 group (n=81) overall (p=0.0008) and when the corresponding sEtOH category was ≥1.00mg/ml (median: 3.195 vs. 1.776μg/ml, p=0.009). A multiple linear regression analysis selected the ALDH2*1/*2 and the sEtOH levels as positive predictors of the sAcH levels (p<0.0001). The enhanced AER in ADH1B*2 carriers and the increased sAcH levels in ALDH2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.