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

BACKGROUND

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.

METHODS

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.

RESULTS

The initial sEtOH levels did not differ between the ADH1B2 group (n = 50) and the ADH1B1/1 group (n = 49) (median: 0.617 vs. 0.762 mg/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 ≥1.00 mg/ml), the median sAER of the ADH1B2 group was 0.075, 0.188, and 0.228 mg/ml/h, respectively, and that of the ADH1B1/1 group was 0.037, 0.115, and 0.233 mg/ml/h, respectively. The sAER of the ADH1B2 group was faster than that of the ADH1B1/1 group overall (p = 0.001) and when the sEtOH category was 0.4 to 0.99 mg/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 ADH1B2 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 ALDH21/1 group (n = 81) overall (p = 0.0008) and when the corresponding sEtOH category was ≥1.00 mg/ml (median: 3.195 vs. 1.776 μg/ml, p = 0.009). A multiple linear regression analysis selected the ALDH21/*2 and the sEtOH levels as positive predictors of the sAcH levels (p < 0.0001).

CONCLUSIONS

The enhanced AER in ADH1B2 carriers and the increased sAcH levels in ALDH21/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.