Association of TNF-α, IL6 and IL-10 gene Polymorphisms with Type 2 Diabetes Mellitus in Relation to Insulin Secretion and Action in Bangladeshi Population

Abstract

Type-2 DM is a polygenic, metabolic illness. It is categorized by prolonged high blood glucose levels as well as unregulated blood pro-inflammatory cytokines by the influence of several genes. A research was conducted on the impact of polymorphism in cytokine genes, with Tumor Necrosis Factor-alpha (TNF-α), Interleukin six (IL—6), and Interleukin ten (IL-10), which consisted of 350 T2DM sufferers and 350 normal healthy controls. The genomic DNA was extracted from the entire blood sample of T2DM affected individuals as well as from control subjects, followed by PCR-RFLP quantification and genotyping using predesigned appropriate primers. The frequency distribution of genotype and allele in T2DM along with controls was examined using SPSS (version 17). Odds ratios (OR) with a 95% confidence interval were established to designate the role of gene polymorphism by the logistic regression analysis. Chisquare tests were analyzed for double and triple combinations of genotypes. Standardized methods were also used to measure the anthropometric (BMI, waist and hip circumferences, waist-hip ratio) and biochemical parameters (FBG, ABF, HBA1C, fasting insulin, total cholesterol, triacylglycerol, LDL-C, HDL-C). It was found that TNF-α G238A, IL-6 A597G, and IL-10 C592A genotypic frequency followed the Hardy Weinberg Equilibrium in a control population. This study showed non-significant variations in age, sex, Body Mass Index, and the Waist-Hip Ratio between T2DM and control. The only homozygous mutant variant of TNF-α, as well as IL-6 gene polymorphisms, were significantly (p<0.001) correlated with T2DM, whereas IL-10 gene polymorphism was significantly (p<0.001) correlated with T2DM in both homozygous and heterozygous mutant variant where OR and 95% CI were 3.02 (1.75 - 5.22), 12.28 (7.17- 21.03) and 15.17 (8.98-25.60) and 2.04 (1.43 -2.91) respectively. Minor allele frequency was significantly correlated with T2DM in all three (TNF- α, IL-6, and IL-10) gene polymorphisms. The double and triple combination of the three genes showed a significant association with T2DM. The study outcomes recommend that specific GAA haplotype was significantly (p<0.05) correlated with type 2DM. Odds of GAA haplotype had 2.01 times more chances to develop T2DM than the control, and 95% CI was (1.58-2.58). Single nucleotide polymorphism of TNF- α G238A, IL-6 A597G, and IL-10 C592A genes were significantly correlated with T2DM.