Association of Tumor Necrosis Factor-alpha Polymorphisms and Risk of Coronary Artery Disease in Patients with Non-alcoholic Fatty Liver Disease

Abstract

Background:Cardiovascular events account for the main cause of death in patients with non-alcoholic fatty liver disease (NAFLD), and are largely influenced by genetic factors. Although multiple studies showed that tumor necrosis factor-alpha (TNF-α) polymorphisms are risk factors in the progression of NAFLD, few papers on the association of the polymorphisms and the developing coronary artery disease (CAD) in NAFLD patients have been reported.Objectives:The present study was designed to evaluate the association of TNF-α polymorphisms at residues -238 and -308, with the risk of developing CAD in Chinese patients with NAFLD.Patients and Methods:The TNF-α polymorphisms at residues 238 and 308 were genotyped in B-type ultrasonography proven NAFLD patients with (n = 246), without (n = 247) CAD and healthy controls (n = 304), using polymerase chain reaction (PCR). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS statistical software, version 20.0 for Mac.Results:We found a significant association between TNF-α-238 guanine to alanine (GA) polymorphism and carriers of variant allele A between NAFLD patients with and without CAD (P < 0.05). Carriers of the A allele of TNF-α-238 had higher serum triglycerides (TG) and low density lipoprotein (LDL) levels in NAFLD patients with CAD (P = 0.025 and 0.001, respectively) and a higher TG level in NAFLD patients without CAD (P = 0.017), than their non-carrier counterparts.Conclusions:In the Chinese Han population that we studied, NAFLD patients who carry the TNF-α-238 GA polymorphism have an increased risk of developing CAD. Mechanisms underlying this potentially important association require further investigation.