Association analysis Of Genetic Polymorphisms (Rs2146323) and (Rs699947) of Vascular Endothelial Growth Factor-A (Vegf-A) In Patients of Type 2 Diabetes Mellitus

Abstract

Type 2 Diabetes mellitus is a disease classified by low production of the hormone insulin and gradual loss of β-cells in the pancreas and chronic resistance to insulin in the body. The gene Vascular Endothelial Factor – A (VEGF-A) is up-regulated as a result of uncontrolled blood glucose levels. VEGF-A has been widely linked with the proliferation of Diabetic Retinopathy (DR) in the patients of DM. The study focuses on identifying the association and risk analysis of two of the most linked polymorphisms of VEGF-A rs2146323 and rs699947 with DM and its co-morbidity DR in a cohort of 106 patients with Type2 Diabetes mellitus in Pakistan. Allele specific PCR was employed to observe the association between polymorphisms and the possible disease pathogenesis. The study showed remarkable association between the polymorphism rs2146323 and T2DM. The heterozygous genotype CA showed susceptibility of developing DR in T2DM vs. control with OR= 3.99, 95% CI= (2.1- 7.4) and P= <0.0001***. The chi square (x2 ) value (46.1) and P= (<0.0001***) suggests a significant association between rs2146323 with T2DM and a risk of developing DR. A relative association between the CA genotype of rs699947 of VEGF-A, and T2DM vs. control was found with OR= 1.9, 95% CI= 1.05-3.52 and P= 0.03. The chi square (x2 ) value (10.10) and P= (0.0064**) shows some association of T2DM co-morbidities with T2DM. The allelic difference in the distribution of alleles for both polymorphisms of VEGF-A studied show no significant difference in their distribution of alleles in T2DM and Controls. Further research with ample sample size is required to validate the findings of this research on a larger set of patient population.