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Genetic Polymorphisms of Alcohol Dehydrogenase‐1 B and Aldehyde Dehydrogenase‐2 and Liver Cirrhosis, Chronic Calcific Pancreatitis, Diabetes Mellitus, and Hypertension Among J apanese Alcoholic Men
Author(s) -
Yokoyama Akira,
Mizukami Takeshi,
Matsui Toshifumi,
Yokoyama Tetsuji,
Kimura Mitsuru,
Matsushita Sachio,
Higuchi Susumu,
Maruyama Katsuya
Publication year - 2013
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.12108
Subject(s) - adh1b , aldh2 , odds ratio , medicine , gastroenterology , alcohol dehydrogenase , allele , aldehyde dehydrogenase , confidence interval , endocrinology , alcohol , genetics , chemistry , biology , biochemistry , dehydrogenase , branched chain alpha keto acid dehydrogenase complex , enzyme , gene
Background The presence of the less‐active form of alcohol dehydrogenase‐ 1B encoded by ADH1B *1/*1 (vs. *2 allele) and active form of aldehyde dehydrogenase‐2 (ALDH2) encoded by ALDH2 *1/*1 (vs. *2 allele) increases the risk of alcoholism in E ast A sians. Methods The subjects in this cross‐sectional survey were 1,902 J apanese alcoholic men (≥40 years) who underwent ADH 1B/ ALDH 2 genotyping. Results Age‐adjusted daily alcohol consumption did not differ according to the ADH 1B/ ALDH 2 genotypes. The age‐adjusted odds ratios ( AOR s; 95% confidence interval) for liver cirrhosis ( LC ; n = 359, 1.58 [1.19 to 2.09]), chronic calcific pancreatitis ( CP ; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus ( DM ; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B *2 allele carriers than in the ADH1B *1/*1 carriers. The AOR s for LC (1.43 [1.01 to 2.02]), CP (1.68 [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension ( HT ; n = 495, 1.52 [1.11 to 2.07]) were higher in the ALDH2 *1/*1 carriers than in the ALDH2 *1/*2 carriers. The ADH1B *2 ‐associated AOR for LC was 2.08 (1.46 to 2.94) among those aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over, and the interaction between ADH 1B genotype and age on the LC risk was significant ( p = 0.009). When the group with non‐ LC and no/mild fibrosis was used as controls, the ADH1B *2 ‐associated AOR s increased according to the severity of their liver disease: 1.67 (1.32 to 2.11) for the group with non‐ LC and serum type IV collagen values ≥200 ng/ml, 1.81 (1.24 to 2.63) for the group of C hild‐ P ugh class A LC , and 3.17 (1.98 to 5.07) for the group with C hild‐ P ugh class B / C LC . Anti‐hepatitis C virus ( HCV ) antibody was positive in 103 patients, and the groups with a high anti‐ HCV antibody titer and either the ADH1B *2/*2 genotype or the ALDH2 *1/*1 genotype had the highest AOR s (8.83 and 4.90, respectively). The population attributable fraction ( PAF ) due to the ADH1B *2 allele was 29% for LC , 47% for CP , and 27% for DM , and the PAF due to the ALDH2 *1/*1 genotype was 26% for LC , 34% for DM , and 30% for HT . Conclusions The ADH1B *2 allele increased the AOR s for LC , CP , and DM of the alcoholics, and the ALDH2 *1/*1 genotype increased their AOR s for LC , DM , and HT . HCV infection and genetic susceptibility had a synergistic effect on the AOR for LC .