The rs4925648, rs121908149 and rs121908152 Genetic Variations in the NLRP3 Inflammasome and Risk of Type 2 Diabetes

Type 2 diabetes (T2DM) is a disease characterized by a complete or partial deficiency of insulin, hyperglycaemia and insulin resistance. Inflammation is the natural defensive response of the organism against any harmful, foreign or destructive effect. Recent studies have emphasized the link between inflammation, insulin resistance and pathogenesis of type 2 diabetes. Inflammasome is a protein complex that recognizes stimulants with the potential to produce inflammation and, in response, processes a process responsible for the production and secretion of proinflammatory cytokines. There are different types of inflammatory structures, but NLRP3 (Nod-like receptor pyrin domain-containing-3) inflammasome has been associated with type 2 diabetes, insulin resistance and obesity. In macrophages, NLRP3 activates inflammation and impairs insulin signaling, causes insulin resistance by TNF-dependent and TNF-independent pathways in cells targeted to insulin. The aim of our study is to investigate the relationship of rs10925027 and rs4925659 variants of the NLRP3 gene. For this purpose, DNA samples isolated from blood samples of 100 T2DM patients and 100 control individuals were genotyped using the Sequenom MassARRAY system and the Iplex GOLD SNP protocol for the NLRP3 rs10925027 and rs4925659 variants and then evaluated with appropriate statistical methods. As a result of our study genotype frequencies of rs4925648 (p=0.108), rs121908149, rs121908152 variants between the risk of T2DM was not statistically significant difference. While there was no individuals with TT genotype which were polymorphic genotypes in the patient and control subjects for rs4925648 site, it was found that CC and CT genotype distributions were similar. But in heterozygous and dominant model rs4925648 site show statistically significant distribution (p=0.048). The all individuals have CC genotype which is ancestral genotype in the rs121908149. Also in the rs121908152 region, all individuals were sequenced as ancestral TT genotype. The genotypic variation of these variants can be interpreted as this region can be a protected region. In conclusion, rs121908149 and rs121908152 variants from the NLRP3 gene in the structure of the inflammasome could not be associated with T2DM risk in patients with Turkish origin while rs4925648 variant was found to be associated with type 2 diabetes