Premium
Effects of ADH 1B and ALDH 2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men
Author(s) -
Yokoyama Akira,
Kamada Yoko,
Imazeki Hiromi,
Hayashi Emiko,
Murata Shigenori,
Kinoshita Kenji,
Yokoyama Tetsuji,
Kitagawa Yoshinori
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13073
Subject(s) - acetaldehyde , aldehyde dehydrogenase , alcohol dehydrogenase , ethanol , saliva , alcohol , medicine , aldh2 , chemistry , endocrinology , biochemistry , enzyme
Background The genetic polymorphisms of alcohol dehydrogenase‐1B ( ADH 1B) and aldehyde dehydrogenase‐2 ( ALDH 2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol ( sEtOH ) levels are well correlated with blood Et OH levels. Methods To study the effects of ADH 1B and ALDH 2 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 ADH 1B*2 group ( n = 50) and the ADH 1B*1/*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 ADH 1B*2 group was 0.075, 0.188, and 0.228 mg/ml/h, respectively, and that of the ADH 1B*1/*1 group was 0.037, 0.115, and 0.233 mg/ml/h, respectively. The sAER of the ADH 1B*2 group was faster than that of the ADH 1B*1/*1 group overall ( p = 0.001) and when the sEtOH category was 0.4 to 0.99 mg/ml ( p < 0.0001). The ADH 1B 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 ADH 1B*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 ALDH 2 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 ALDH 2*1/*2 group ( n = 18) was higher than that of the ALDH 2*1/*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 μ g/ml, p = 0.009). A multiple linear regression analysis selected the ALDH 2*1/*2 and the sEtOH levels as positive predictors of the sAcH levels ( p < 0.0001). Conclusions The enhanced AER in ADH 1B*2 carriers and the increased sAcH levels in ALDH 2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.