Association of EGF A61G polymorphism and EGF expression with type 2 diabetes mellitus in Indian population

Abstract

BackgroundEpidermal Growth Factor (EGF) plays critical role in regeneration of pancreatic β-cells and insulin secretion. The deficiency in EGF expression affects pancreatic β-cell's proliferation, maintenance and its function like insulin secretion which may result in individual susceptibility to Type 2 Diabetes Mellitus (T2DM). EGF A61G is a functional SNP that modulate EGF levels and eventually affects activity of β-cells. ObjectiveThe present study explores EGF A61G polymorphism (rs4444903) and correlates it with the risk of developing T2DM and mRNA expression. MethodsThe study included 90 subjects, T2DM patients (n = 30) and healthy controls (n = 60). Blood sample was collected from subjects to study EGF A61G polymorphism by PCR-RFLP and EGF mRNA expression level by Real-time PCR. ResultsThe EGF gene A61G polymorphism was found to be in significant association with T2DM. A/G genotype (OR = 4.07, 95%CI = 1.303 to 12.71, p = 0.0206) and ‘A’ allele (OR = 1.91, 95%CI = 1.017 to 3.568, p = 0.043) were significantly associated with risk of T2DM. The prevalence of allele ‘A’ was found to be higher in diabetic males and females (52.5% and 55% respectively). As compared to healthy subjects EGF mRNA expression levels showed significant down-regulation in T2DM patients (p = 0.005). The relative EGF mRNA expression in A/A and A/G genotype was significantly lower than G/G genotype. ConclusionThe present study suggests that EGF gene A61G polymorphism may be a genetic risk factor for susceptibility of T2DM in Indian population. However, this marker deserves further investigation using more sample size.