Association of Apolipoprotein E Polymorphisms in Patients with Non-Alcoholic Steatohepatitis

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.

Alcohol drinking patterns and the risk of fatty liver in Japanese men

“…Elevations in HDL cholesterol levels confer a lower risk of chronic heart disease [16]. Recently, studies examining the pathogenesis of NASH have demonstrated an association of hepatic apolipoprotein synthesis/secretion with the development of steatosis [31,32]. Our study provides evidence that the risk of FL is decreased across the categories of alcohol consumption, despite an increase in serum triglyceride levels.…”

The Incapacity of the Surgeon to Identify NASH in Bariatric Surgery Makes Biopsy Mandatory

“…Sazci et al found VLDL levels significantly higher in NASH patients compared with the healthy controls [18]. These authors also demonstrated an association between VLDL and hypertriglyceridaemia and between apolipoprotein E (APOE) polymorphism and VLDL [18]. The most likely reason for increased VLDL level in NASH patients could be explained based on a previous study by Huang et al [19].…”

“…Stored triglycerides in adipose tissue and those newly synthesized within the liver through de novo lipogenesis are the major sources of triglycerides in the liver, and major routes of triglyceride elimination from the liver are fatty acid β-oxidation and the secretion of VLDL [17]. Sazci et al found VLDL levels significantly higher in NASH patients compared with the healthy controls [18]. These authors also demonstrated an association between VLDL and hypertriglyceridaemia and between apolipoprotein E (APOE) polymorphism and VLDL [18].…”

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis

“…22,23 LDLR or ApoE single-knockout mice developed some of the NAFLD characteristics [24][25][26] but generally failed to broadly reflect the whole spectrum of NAFLD key features. As such, ApoE À / À mice on a fat-and cholesterol-enriched diet developed hepatic inflammation but only mild steatosis.…”