Stojan Kariž1, Daniel Petrovič2. 1. Internal Department, General Hospital Izola, Polje 35, 6310 Izola, Slovenia. Electronic address: stojan.kariz@siol.net. 2. Institute of Histology and Embryology, Medical Faculty of Ljubljana, Korytkova 2, 1105 Ljubljana, Slovenia.. Electronic address: daniel.petrovic@mf.uni-lj.si.
Abstract
OBJECTIVE: Vascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM). DESIGN AND METHODS: The association of KDR -604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case-control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD. RESULTS: A significantly higher frequency of the CC genotype of the KDR -604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p=0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the -604CC genotype compared to those with other (CT+TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p<0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the -604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR=1.6; 95% CI=1.1-2.1; p=0.022). CONCLUSION: The present study demonstrates that the CC genotype of the KDR -604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.
OBJECTIVE:Vascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM). DESIGN AND METHODS: The association of KDR -604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case-control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD. RESULTS: A significantly higher frequency of the CC genotype of the KDR -604T>C (rs2071559) polymorphism was found in diabeticpatients with MI compared to diabeticpatients without CAD (27.5% vs. 21.1%, p=0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the -604CC genotype compared to those with other (CT+TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p<0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the -604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR=1.6; 95% CI=1.1-2.1; p=0.022). CONCLUSION: The present study demonstrates that the CC genotype of the KDR -604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.
Authors: Nora M Schacher; Dorette Raaz-Schrauder; Francesca Pasutto; Florian M Stumpfe; Miyuki Tauchi; Barbara Dietel; Stephan Achenbach; Katharina Urschel Journal: Int J Mol Med Date: 2019-08-05 Impact factor: 4.101