Connection between Il-6 -174g> C Polymorphism and Type II Diabetes

It is widely recognized that obesity and type II diabetes are associated with meaningful metabolic alterations and low grade inflammation. The last one is due to increase of proinflammatory M1 macrophages in adipose tissues that is accompanied with secretion of the wide spectrum of proinflammatory cytokines and adipocytes, leading to insulin resistance and metabolic syndrome development. One of the most influential factors is interleukin 6 (ІL-6). The number of evidences proved the role of IL 6 in type II diabetes pathogenesis. IL-6 hyper production could be caused by single nucleotide polymorphism in IL gene promoter, known as -174G> C polymorphism. On the other hand, there are numerous data demonstrating the same polymorphism role in obesity, cancer, coronary artery diseases etc. Thus, it is important to examine whether -174G> C polymorphism demonstrate specific relations with T2D complications development, such as: diabetic polyneuropathy, retinopathy, nephropathy or diabetic food syndrome with ulcers. The purpose of the study was to examine the relationship between IL-6 -174G> C polymorphism and T2D and its clinical and laboratory manifestations development. 120 patients with T2D and 66 non-diabetic patients were examined. Genomic DNA extraction was performed using QIAamp DNA Blood Mini Kit (QIAGEN, USA) with manufacturer guideline. IL-6 genotyping for polymorphous site 174G>C (rs1800795) was conducted with Real-Time PCR, using test-systems TaqMan Mutation Detection Assays Thermo Fisher Scientific (USA). To compare the genotypes with T2D phenotypes we considered such complications of T2D as peripheral polyneuropathy, diabetic retinopathy, diabetic nephropathy, and diabetic foot syndrome. In addition, the indicators of cardiovascular risks including blood pressure, signs of atherosclerosis, coronary heart disease, and angioplasty of the lower extremities were concerned. In addition, lipidogram data, levels of insulin and C-reactive protein were taken into account when comparing data of patients with different genotypes. The frequency difference between genotypes was evaluated using χ2 test. The connection between different genotypes and clinical and laboratory data was judged according to the ratio of risks (OR), taking into account the 95% confidence interval. The relationship between IL-6-174G>C polymorphism and the development of T2D was revealed: the GG genotype at the IL-6-174G>C site was associated with an increased risk of T2D development (OR=2.52; 95% CI 1,24-5,13; P=0.011). Comparison of laboratory parameters reflecting the peculiarities of carbohydrate and lipid metabolism in T2D patients revealed that GG genotype is associated with hyperglycemia and hyperinsulinemia (P = 0.0125), as well as higher levels of triglycerides (P = 0.046) and total cholesterol (P = 0,0326). However, the relationship between the IL-6-174G>C polymorphism and such complications of T2D as polyneuropathy, retinopathy, nephropathy, diabetic foot syndrome development was not found. In conclusion, research results suggest that homozygous carriers of pro-inflammatory ‘G' allele of IL6-174G > C polymorphism may be more susceptible to Type II diabetes, supporting the relevance of inflammatory pathways, metabolic alterations and insulin resistance as well. However, specific links between IL-6-174G>C polymorphism and T2D complications were not found.