Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: case-control cross-sectional study

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.