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.
