Akira Yokoyama1, Nobuhito Taniki2, Sachiko Hara3, Emiko Haysashi3, Nobuhiro Nakamoto2, Takeshi Mizukami3, Katsuya Maruyama3, Tetsuji Yokoyama4. 1. National Hospital Organization Kurihama Medical and Addiction Center, 5-3-1 Nobi, Yokosuka, Kanagawa, 239-0841, Japan. a_yokoyama@kurihama1.hosp.go.jp. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. 3. National Hospital Organization Kurihama Medical and Addiction Center, 5-3-1 Nobi, Yokosuka, Kanagawa, 239-0841, Japan. 4. Department of Health Promotion, National Institute of Public Health, 2-3-6 Minami, Wako, Saitama, 351-0104, Japan.
Abstract
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.
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 ADH1BArg/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 ADH1BArg/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.
Entities:
Keywords:
Acetaldehyde; Alcohol dehydrogenase-1B; Aldehyde dehydrogenase-2; Body mass index; Cirrhosis; Fatty liver
Authors: H W Goedde; D P Agarwal; G Fritze; D Meier-Tackmann; S Singh; G Beckmann; K Bhatia; L Z Chen; B Fang; R Lisker Journal: Hum Genet Date: 1992-01 Impact factor: 4.132
Authors: L J Bierut; A M Goate; N Breslau; E O Johnson; S Bertelsen; L Fox; A Agrawal; K K Bucholz; R Grucza; V Hesselbrock; J Kramer; S Kuperman; J Nurnberger; B Porjesz; N L Saccone; M Schuckit; J Tischfield; J C Wang; T Foroud; J P Rice; H J Edenberg Journal: Mol Psychiatry Date: 2011-10-04 Impact factor: 15.992