Abstract 19698: The Impact of Genetic Variability of eNOS on Progression of Microvascular Disease in Type 2 Diabetes Patients: Effects on Angiogenesis Mechanisms
Introduction: Microvascular disease of type 2 diabetes (T2D) patients progresses despite strict glycaemic control, and the mechanisms are poorly understood. Endothelial dysfunction and adiponectin are pivotally involved in the pathogenesis of vascular disease.
Hypothesis: We hypothesised that genetic variability on endothelial nitric oxide synthase (eNOS) and adiponectin gene (ADIPOQ) are associated with the progression of microvascular disease in T2D patients.
Methods: Two hundred and twenty (n=220) T2D outpatients were enrolled in this study. Participants were assessed at baseline for presence of diabetic foot or diabetic retinopathy by specialists. Blood samples were drawn for estimation of MDRD eGFR and measurement of vascular endothelial growth factor (VEGF) and for genotyping for single nucleotide polymorphisms (SNP) T786C and G894T on eNOS gene and T45G and G276T on ADIPOQ. Patients were re-assessed at 30months for progression of diabetic microangiopathy (defined as development of new diabetic foot, new diabetic retinopathy and/or decline in MDRD eGFR>25%).
Results: There was no association of T45G, G276T and G894T SNPs with VEGF (p=NS for all). However homozygotes for CC on T786C had higher levels of VEGF (CT/TT: 383.3±43.6pg/mL vs CC: 586.5±91.8pg/mL, p<0.05). T786C SNP was significantly associated with the progress of microvascular disease; carriers of the 786C allele had increased odds ratio for the composite endpoint (OR=2.462, 95%CI:1.082-5.601,p<0.05) compared to other allele groups. There was no association between T45G, G276T, G894T SNPs and microvascular disease progression.
Conclusions: We demonstrate that C homozygotes on T786C SNP had increased odds ratio for development of new diabetic foot, new diabetic retinopathy or decline in renal function at 30 months. This reported interaction between genetic variability on eNOS gene and progress of diabetic microangiopathy, possibly via effects on angiogenesis mechanisms, warrants further investigation.
Author Disclosures: T. Konsola: None. A. Antonopoulos: None. G. Siasos: None. C. Kollia: None. N. Gouliopoulos: None. E. Oikonomou: None. E. Kassi: None. M. Moschou: None. N. Tentolouris: None. D. Tousoulis: None.
- © 2016 by American Heart Association, Inc.