Association Between the ANGPT2 rs2442598 Polymorphism and Diabetic Nephropathy in Slovenian Patients with Type 2 Diabetes Mellitus

Background: The aim of our study was to evaluate the association of angiopoietin 2 (ANGPT2) rs2442598 and vascular endothelial growth factor A (VEGFA) rs2010963 with diabetic nephropathy (DN) in Slovenian subjects with type 2 diabetes mellitus (T2DM). Angiopoietin–endothelial tyrosine kinase receptor (Ang-Tie2) and VEGF-A signaling regulate glomerular endothelial stability and permeability and may contribute to DN susceptibility. Methods: We conducted a case–control study including 897 unrelated Slovenian subjects with T2DM (344 DN cases; 553 long-standing T2DM controls without DN). ANGPT2 rs2442598 and VEGFA rs2010963 were genotyped using TaqMan assays. Genetic associations were analysed using co-dominant, additive, dominant, and recessive genetic models with logistic regression adjusted for waist circumference, systolic blood pressure, fasting glucose, and triglycerides. Results: ANGPT2 rs2442598 was significantly associated with DN, with increased risk in carriers of the C allele, including a significant additive per allele effect (OR 1.39, 95% CI 1.10–1.74) and a dominant model effect (OR 1.47, 95% CI 1.11–1.96). In contrast, VEGFA rs2010963 showed no evidence of association across genetic models. Conclusions: In Slovenian patients with T2DM, ANGPT2 rs2442598 is associated with DN, whereas VEGFA rs2010963 is not. This association suggests that ANGPT2 genetic variation may influence DN risk and supports further functional work to define the biological effects of rs2442598.