Tetiana Tyzhnenko

SI “V. Danilevsky Institute of Endocrine Pathology Problems of NAMS of Ukraine”; Kharkiv, Ukraine

Presentation title: Investigation of single-nucleotide polymorphisms association in patients with type 2 diabetes mellitus complicated nonalcoholic fatty liver disease

Abstract:

  From the point of view of modern medicine, adipose tissue functions as an endocrine organ, secretes certain cytokines called "adipocytokines", such as adiponectin, leptin, tumor necrosis factor-α (TNF-α, tumor necrosis factor-alpha - TNFα) and so on. Chemical signals from white adipose tissue are believed to be directly related to IR and inflammation, therefore it is expected that circulating levels of adipokines may be useful as biomarkers for risk assessment and other pathological conditions associated with obesity, for example, such as non-alcoholic fatty liver disease (NAFLD). NAFLD has become a major health problem in developed countries, affecting more than 30% of the total population. NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus (T2D), hyperlipidemia. The pathogenesis of NAFLD includes a number of factors, and several interrelated mechanisms, such as insulin resistance, lipotoxicity, imbalance of inflammatory mediators, endotoxinemia, and others. NAFLD is defined as a disease with a genetic predisposition. The role of genetic variants in NAFLD, particularly single nucleotide polymorphisms (SNPs), has been the focus of extensive research in the last decade, including the classic candidate gene association study. It has been established that genes play a significant role in susceptibility to NAFLD and its progression. It is believed that gene polymorphisms in patients with NAFLD are associated with a large number of substances involved in the metabolism of fats and carbohydrates in the liver. We have analyzed effects of single nucleotide polymorphisms of the adipokines genes polymorphism taking into account them circulating levels in patients with type 2 diabetes mellitus in the presence / absence of nonalcoholic fatty liver disease and its possible impact on the disease. 1. Thus, as a result of research on the association of haplotypes and polymorphic variants of the adiponectin gene with NAFLD in type T2D in the Kharkiv population have been established new markers (rs1501299 G-allele, rs2241766 and rsl501299 GGGG and GTGG haplotypes, respectively) of an increased risk of NAFLD developing in type T2D patients. 2. 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 association of NAFLD with genotypes containing low-productivity alleles of TNF-α has not been established. 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. 3. Our study showed that women with type 2 diabetes mellitus carrying the GG genotype with the G-2458A polymorphic variant of the LEP gene have 3.4 times higher leptin levels than men carrying the same genotype (p<0.03). It is necessary to continue work to identify the functional role of the studied LEP gene polymorphism and its possible associations with indicators of hormonal and metabolic components of insulin resistance in the development of non-alcoholic fatty liver disease in the presence of type 2 diabetes under the conditions of increasing the sample. Prospects for further research should be based on the study of the role of other candidate genes in the development of NAFLD and their relationship with various metabolic parameters, which will allow to clarify the role of genes in the formation of NAFLD in the Ukrainian population.