The Center for Diagnosis and Treatment of Noninfectious Liver Disease, Institute of Alcoholic Liver Disease, Beijing, China.
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.
Am J Med Sci. 2018 Jul;356(1):10-14. doi: 10.1016/j.amjms.2018.03.012. Epub 2018 Mar 20.
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.
ALDH2 genotyping was performed in 535 healthy controls and 281 patients with ALD.
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).
Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.
只有一部分酗酒患者会发展为酒精性肝病（ALD），尽管确切的机制尚未完全阐明。酒精进入人体后，由两种关键的氧化酶——乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）进行代谢。ALDH 有两种主要的同工酶形式，即胞质型和线粒体型，分别由醛脱氢酶 ALDH1 和 ALDH2 基因编码。ALDH2 基因被认为会改变对酒精依赖和酒精性肝损伤的遗传易感性。本研究旨在确定乙醛脱氢酶 2（rs671）Glu504Lys 多态性与 ALD 的关系。
对 535 名健康对照者和 281 例 ALD 患者进行 ALDH2 基因分型。
ALD 患者中常见的单核苷酸多态性 rs671 504Glu（Glu/Glu）的发生率（95.4%）明显高于对照组（73.7%，P<0.0001）。在对照组中，杂合子（Glu/Lys）基因型的比例为 23.7%，而 ALD 患者中仅为 4.6%（比值比[OR] = 0.16，95%可信区间：0.09-0.28）。ALD 患者 504Lys 等位基因的频率为 2.3%，而健康对照组为 14.5%（OR = 0.13，95%可信区间：0.07-0.24）。
使用基因型和等位基因分析，与携带 ALDH2 504Glu 变异的患者相比，携带 ALDH2 504Lys 变异的患者发生 ALDH2 的相关性更低。
