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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

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.

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Abbreviations

AceCS1:

Acetyl-CoA synthetase-1

ADH1B:

Alcohol dehydrogenase-1B

ALDH2:

Aldehyde dehydrogenase-2

AMPK:

AMP-activated protein kinase

BMI:

Body mass index

CI:

Confidence interval

CYP2E1:

Cytochrome P4502E1

LSM:

Least square mean

OR:

Odds ratio

PPARα:

Peroxisome proliferator-activated receptor α

SERBP-1:

Sterol regulatory element-binding protein-1

TCA:

Tricarboxylic acid

VLDL:

Very low density lipoprotein

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Acknowledgements

We thank Minori Tsukahara for her expert technical assistance.

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Authors and Affiliations

  1. National Hospital Organization Kurihama Medical and Addiction Center, 5-3-1 Nobi, Yokosuka, Kanagawa, 239-0841, Japan

    Akira Yokoyama, Sachiko Hara, Emiko Haysashi, Takeshi Mizukami & Katsuya Maruyama

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan

    Nobuhito Taniki & Nobuhiro Nakamoto

  3. Department of Health Promotion, National Institute of Public Health, 2-3-6 Minami, Wako, Saitama, 351-0104, Japan

    Tetsuji Yokoyama

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  1. Akira Yokoyama
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Correspondence to Akira Yokoyama.

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Yokoyama, A., Taniki, N., Hara, S. et al. Slow-metabolizing ADH1B and inactive heterozygous ALDH2 increase vulnerability to fatty liver in Japanese men with alcohol dependence. J Gastroenterol 53, 660–669 (2018). https://doi.org/10.1007/s00535-017-1402-6

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  • DOI: https://doi.org/10.1007/s00535-017-1402-6

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