Effects of genetic variations in the genes encoding NOD1 and NOD2 on type 2 diabetes mellitus and insulin resistance

What is known and objectiveNucleotide-binding oligomerization domain (NOD) 1 and NOD 2 are members of the NOD-like receptor (NLR) family and contain a caspase recruitment domain. NLRs are located in the cytosol, bind bacterial and viral ligands and play a key role in the realization of innate and adaptive immune response, inflammation, apoptosis and reactive oxygen species generation. Insulin resistance (IR) is a leading cause of type 2 diabetes mellitus (T2DM) and associated with obesity, inflammation and pro-inflammatory responses. NOD1 and NOD2 gene variants may affect the risk of chronic inflammation, insulin resistance and T2DM by shifting the balance between pro- and anti-inflammatory cytokines. The aim of our study was to determine whether the NOD1/2 gene variants might contribute to the risk of T2DM and IR. MethodsThe rs5743336 variant of NOD1 and rs2066847 variant of NOD2 were analysed by PCR-RFLP analysis in 200 subjects (T2DM: n = 100; healthy controls: n = 100) of Turkish origin. PCR products were digested with the AvaI and ApaI restriction enzymes. For the NOD1 site, the presence of the G allele was indicated by cleavage of the 379 bp amplified PCR product that yielded 209-bp and 170-bp fragments. For the NOD2 site, 151-bp PCR products were cleaved and yielded 130-bp and 21-bp fragments when the WT-insC mutation was present. Comparisons of the genotypes between controls and patients were performed by chi-square tests. Results and discussionThe genotypes of the rs5743336 variant of NOD1 and the rs2066847 variant of NOD2 are presented, and no significant differences were observed in the genotype frequencies of the NOD1 and NOD2 variants between the healthy controls and T2DM patients (P > 0<bold></bold>05). According to our preliminary data, NOD1/2 gene variants are not linked with T2DM and IR. What is new and conclusionThis study is the first to look for possible association of the genotype frequencies of NOD1 and NOD2 genes with T2DM and IR. The significant finding of this report is that the rs5743336 and rs2066847 variations in the NOD1/2 gene are not associated with T2DM and IR risk in patients of Turkish origin.