The Polymorphism -308 G/a of the TNF Gene and Metabolic Imbalance in Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease, Taking Into Account Cardiovascular Complications

Abstract

Non-alcoholic fatty liver disease (NAFLD), the most common form of liver disease, is now recognized as a major public health problem worldwide. Tumor necrosis factor alfa (TNF-α), a member of the TNF/TNFR cytokine family, is an intercellular transmission molecule that has been reported in a wide range of human noninfection diseases. The aim of the study was to determine the circulating levels of TNF-α and the nature of its relationships with the components of insulin resistance, both metabolic and hormonal, in patients with type 2 diabetes; and establishing the nature of cardiovascular complications (taking into account TNF-α gene polymorphism) in the presence and absence of NAFLD. Materials and methods. Case-control study included information about 50 practically healthy people from the city of Kharkiv and the region. The examined population (except control subjects) consisted exclusively of patients with type 2 diabetes mellitus with a long-term existence of the disease against the background of metabolic syndrome, with varying degrees of glycemic control and violations of liver homeostasis in the absence of renal failure. 117 people were selected for analysis: 63 of them with type 2 diabetes in the presence of NAFLD and 54 patients with type 2 diabetes without NAFLD. Genotyping for single nucleotide polymorphism -308 G>A of the TNF-α was performed by the method of polymerase chain reaction with appropriate primers and NcoI endonuclease. Testing of statistical hypotheses was carried out using the odds ratio and χ2 criteria at the significance level of P≤0.05. Results. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G>A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus. No association of the studied polymorphism with the risk of developing NAFLD was found. The obtained data make it possible to assume that the studied polymorphism -308 G>A of the TNFα gene is more associated with the risk of developing type 2 diabetes, and the occurrence or progression of NAFLD primarily depends on metabolic imbalance, and not on the contribution of the studied polymorphism. Conclusions. Non-alcoholic fatty liver disease is closely related to hormonal and metabolic risk factors and markers of cardiovascular disease and type 2 diabetes and may increase the risk of developing and progressing cardiovascular complications. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G>A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus.