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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

Type2 diabetes mellitus is a metabolic, pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines suggesting a causal role of inflammation in its etiology. Polymorphism of cytokine genes including tumour necrosis factor alpha (TNF-α), interleukin-6(IL-6) and interleukin 10(IL-10) were studied in 350T2DM patients as well as in 350 normal healthy controls. Genomic DNA was isolated from both T2DM patients and controls followed by quantification and genotyping by polymerase chain reaction-restriction fragment length polymorphism using suitable primers. Double and triple combinations of genotypes were analyzed by chi square test. Gene -gene interaction and linkage disequilibrium tests were performed using SHEsis software. Individually IL-6A/G &IL-10C/A had showed significant association with lower risk whereas only TNF-α G/A homozygous mutant variant showed higher risk of association with T2DM.In double combinations of TNF-α AA, IL-6AA genotypes increased the risk of DM 2.16 times(1.25 to 3.747) and IL-6 GG &IL-10 AA genotypes increased the risk of DM up to 3.16 times and in triple combinations TNF-alpha AA, IL-6 GG, IL-10 AA genotypes increased the risk of T2DM up to 1.75 times((0.064 to 0.457). My results suggest that individual having a GAC haplotype showed significantly increased the risk of T2DM up to 2.018 times (1.582 to 2.576)

 Roksana Yeasmin

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