Association Between Aldehyde Dehydrogenase 2 Glu 504 Lys

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 o 0.0001). Among controls, 23.7% had the heterozygous (glu/lys) genotype compared to 4.6% in those with ALD (odds ratio [OR]1⁄4 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 1⁄4 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. Key Indexing Terms: Aldehyde dehydrogenase; Gene polymorphism; Alcoholic liver disease; Risk. [Am J Med Sci 2018;] (]):]]]–]]].] INTRODUCTION Excessive alcohol drinking is one of the most significant risk factors for health problems such as injuries, liver diseases and cancer. Drinking becomes excessive when it causes or elevates the risk for alcohol-related problems or complicates the management of other health problems. According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), excessive drinking is defined as men who drink thern Society for Clinical Investigation. Published by Els www.ssciweb.org more than 4 standard drinks in a day (or more than 14 per week) and women who drink more than 3 drinks in a day (or more than 7 per week). Alcoholic liver disease (ALD) is a major adverse health event resulting from excessive drinking. Its pathogenesis is a multistep process consisting of a series of histopathologic changes. More than 90% of drinkers develop alcoholic steatosis which is reversible upon abstinence. However, if excessive alcohol use continues, the disease evier Inc. All rights reserved. 1