Slow-metabolizing ADH1B and inactive heterozygous ALDH2 increase vulnerability to fatty liver in Japanese men with alcohol dependence

• Published in: Journal of gastroenterology 2018-05, Vol.53 (5), p.660-669
• Main Authors: Yokoyama, Akira, Taniki, Nobuhito, Hara, Sachiko, Haysashi, Emiko, Nakamoto, Nobuhiro, Mizukami, Takeshi, Maruyama, Katsuya, Yokoyama, Tetsuji
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Acetaldehyde; Adult; Age Factors; Aged; Alcohol dehydrogenase; Alcohol Dehydrogenase - genetics; Alcohol use; Alcoholic beverages; Alcoholism - complications; Aldehyde dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial - genetics; Biliary Tract; Body fat; Body Mass Index; Body weight; Care and treatment; Cirrhosis; Colorectal Surgery; Dehydrogenases; Drinking of alcoholic beverages; Drug dependence; Ethanol; Fat metabolism; Fatty liver; Fatty Liver, Alcoholic - diagnostic imaging; Fatty Liver, Alcoholic - etiology; Fatty Liver, Alcoholic - genetics; Gastroenterology; Genotypes; Hepatology; Heterozygote; Humans; Japan; Lipid metabolism; Liver; Liver cirrhosis; Male; Medicine; Medicine & Public Health; Metabolism; Middle Aged; Multivariate analysis; Original Article—Liver; Pancreas; Physiological aspects; Substance abuse; Surgical Oncology; Time Factors; Ultrasonography; Ultrasound; Ultrasound imaging
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-017-1402-6

Background Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B; rs1229984, His48Arg) and aldehyde dehydrogenase-2 (ALDH2; rs671, Glu504Lys) affect body weight, body fat, and lipid metabolism in individuals with alcohol dependence, and the aim of this study was to identify their determinants in relation to the development of fatty liver. Methods We evaluated associations between the presence of fatty liver and ADH1B and ALDH2 genotypes and other factors in 1604 Japanese men who had been admitted for treatment of alcohol dependence. Results Fatty liver was diagnosed when ultrasonography showed both hepatorenal contrast and liver brightness. Age-adjusted usual alcohol intake did not differ according to ADH1B or ALDH2 genotypes. A multivariate analysis showed that the adjusted odds ratio (OR, 95% confidence interval) of slow-metabolizing ADH1B Arg/Arg carriers was 1.61 (1.27–2.03) for fatty liver and 1.82 (1.37–2.41) for fatty liver with deep attenuation in comparison with the ADH1B His/Arg or His/His carriers, and that the OR of inactive heterozygous ALDH2 Glu/Lys carriers was 1.43 (1.08–1.91) for fatty liver and 1.84 (1.31–2.59) for fatty liver with deep attenuation in comparison with the ALDH2 Glu/Glu carriers. Younger age, shorter interval between the last drink and the ultrasound examination, larger body mass index, and absence of cirrhosis were identified as other positive determinants for fatty liver. Conclusions The ADH1B Arg/Arg genotype and the ALDH2 Glu/Lys genotype were positive determinants of fatty liver in the subjects. These results suggest that slow ethanol and acetaldehyde metabolism accelerates the development of alcoholic fatty liver in heavy drinkers.