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Am J Med Sci. 2018 Jul;356(1):10-14. doi: 10.1016/j.amjms.2018.03.012. Epub 2018 Mar 20.

Association Between Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism and Alcoholic Liver Disease.

Author information

1
The Center for Diagnosis and Treatment of Noninfectious Liver Disease, Institute of Alcoholic Liver Disease, Beijing, China.
2
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana; Eskenazi Health, Indianapolis, Indiana.
3
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
4
Department of Physiology and Neurobiology, and The Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, Connecticut; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
5
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana; Roudebush Veterans Administration Medical Center, Indianapolis, Indiana. Electronic address: zszou302@163.com.
6
The Center for Diagnosis and Treatment of Noninfectious Liver Disease, Institute of Alcoholic Liver Disease, Beijing, China. Electronic address: zszou302@163.com.

Abstract

BACKGROUND:

Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD.

METHODS:

ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD.

RESULTS:

The prevalence of the common form of the single nucleotide polymorphism rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, P < 0.0001). Among controls, 23.7% had the heterozygous (glu/lys) genotype compared to 4.6% in those with ALD (odds ratio [OR] = 0.16, 95% CI: 0.09-0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%, compared to 14.5% in healthy controls (OR = 0.13, 95% CI: 0.07-0.24).

CONCLUSIONS:

Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.

KEYWORDS:

Alcoholic liver disease; Aldehyde dehydrogenase; Gene polymorphism; Risk

PMID:
29779728
PMCID:
PMC6063768
[Available on 2019-07-01]
DOI:
10.1016/j.amjms.2018.03.012

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