Original Articles
Madhukar Saxena, Neena Srivast
Abstract
Type 2 diabetes mellitus (T2DM) is a complex disease characterized by elevated systemic glucose concentrations. Multiple loci pre-disposing to T2DM have emerged from genome-wide association studies. The IL-1 family consists of two pro-inflammatory cytokines viz. IL-1α, IL-1β and a naturally occurring anti-inflammatory agent, IL-1 receptor antagonist (IL-1Ra or IL-1RN). It is known fact that prolonged exposure of human islets to high glucose trigger IL-1b production by b-cells themselves leading to nuclear factor activation and upregulation of Fas signaling thus triggering “autocrine apoptosis”. IL-18 is closely related to IL-1b in structure and in the requirement of caspase-1 to cleave its precursor into an active cytokine. DNA was isolated from venous blood samples, quantified and subjected to Polymerase Chain Reaction-Restriction Fragment Length Polymorphism using suitable primers and restriction endonucleases. The genotypic, allelic and carriage rate frequencies were analyzed for three genetic variants IL-1b (-511 C/T), IL-18 (-607 A/C) and IL-1Ra VNTR (intron 2) in patients and controls using SPSS software. Odd ratios (OR) with 95% confidence interval (CI) was determined to describe the strength of association by logistic regression model. All studied SNPs showed significant association (P<0.001) with occurrence of T2DM and biochemical parameters as well. However, in haplotypic analysis, none of the combinations of alleles showed significant association. Interestingly, it was observed that alleles I and II of IL-1Ra might be involved in T2DM predisposition. The study will probably increase our insight into the proposed impact of IL-1 in the development and/or progression of T2DM and its susceptibility in North-Indian population.