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非酒精性脂肪性肝炎患者载脂蛋白E基因多态性的相关性研究

Association of apolipoprotein E polymorphisms in patients with non-alcoholic steatohepatitis.

作者信息

Sazci Ali, Akpinar Gurler, Aygun Cem, Ergul Emel, Senturk Omer, Hulagu Sadettin

机构信息

Department of Medical Biology and Genetics, Faculty of Medicine, University of Kocaeli, Umuttepe, Kocaeli, 41380, Turkey.

出版信息

Dig Dis Sci. 2008 Dec;53(12):3218-24. doi: 10.1007/s10620-008-0271-5. Epub 2008 May 9.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of alcohol abuse worldwide. Non-alcoholic steatohepatitis (NASH) is the most progressive form of NAFLD. The aim of this study was to investigate the role of apolipoprotein E (APOE) polymorphisms in the development of NASH. We analysed 57 NASH patients and 245 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a case-control study. The diagnosis of the patients was based on liver biopsy. The serum levels of glucose, lipids, vitamin B12, folic acid, homocysteine, insulin, total biluribin, total protein, albumin, ferritin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined in all of the subjects. Body mass index (BMI), waist circumference (WC), AST, ALT, fasting blood sugar (FBS), total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, insulin and ferritin levels were significantly higher in the 57 patients with NASH compared with the 245 healthy controls. The APOE epsilon3 allele was overrepresented in the whole group of NASH patients (epsilon3=97.37% in NASH versus 82.45% in controls). The APOE polymorphism was statistically significantly associated with NASH (chi(2)=15.741; p=0.008). The APOE3/3 genotype (odds ratio [OR]=7.941; p=0.000) was strongly associated with increased risk for NASH in all NASH patients. Consequently, the APOE3/3 genotype may play a role in the aetiopathogenesis of NASH.

摘要

非酒精性脂肪性肝病(NAFLD)是全球范围内在无酒精滥用情况下肝脏脂肪变性异常的最常见原因。非酒精性脂肪性肝炎(NASH)是NAFLD最严重的形式。本研究的目的是探讨载脂蛋白E(APOE)基因多态性在NASH发生发展中的作用。在一项病例对照研究中,我们采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析了57例NASH患者和245例健康对照。患者的诊断基于肝活检。测定了所有受试者的血糖、血脂、维生素B12、叶酸、同型半胱氨酸、胰岛素、总胆红素、总蛋白、白蛋白、铁蛋白、天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平。与245例健康对照相比,57例NASH患者的体重指数(BMI)、腰围(WC)、AST、ALT、空腹血糖(FBS)、总胆固醇、甘油三酯(TG)、低密度脂蛋白(LDL)胆固醇、极低密度脂蛋白(VLDL)胆固醇、胰岛素和铁蛋白水平显著升高。APOE ε3等位基因在整个NASH患者组中占优势(NASH患者中ε3 = 97.37%,而对照组中为82.45%)。APOE基因多态性与NASH在统计学上显著相关(χ2 = 15.741;p = 0.008)。APOE3/3基因型(优势比[OR]=7.941;p = 0.000)与所有NASH患者发生NASH的风险增加密切相关。因此,APOE3/3基因型可能在NASH的发病机制中起作用。

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