The VEGFA rs2010963 Gene Polymorphism Is a Potential Genetic Risk Factor for Myocardial Infarction in Slovenian Subjects with Type 2 Diabetes Mellitus

Abstract

Coronary artery disease (CAD) is a life-threatening condition caused by the chronic gradual narrowing of the lumen of the blood vessels of the heart by atherosclerotic plaque with a strong genetic component. The aim of our study was to investigate the association between the VEGFA polymorphism rs2010963 and myocardial infarction in patients with type 2 diabetes, as well as the expression of VEGFA. A total of 1589 unrelated Caucasians with T2DM lasting longer than 10 years were divided into two groups: case group subjects with MI (484) and a control group without a history of CAD (1105). A total of 25 endarterectomy sequesters were immunohistochemically stained to assess VEGFA expression. The rs2010963 polymorphism of the VEGFA gene was genotyped using a KBioscience Ltd. competitive allele-specific fluorescence-based PCR (KASPar) assay. The C allele was significantly more common in the case group according to the dominant model of inheritance (CC + CG vs. GG) (OR: 1.32; 95% CI: 1.05-1.66; p = 0.0197). A statistically significantly higher numerical areal density of VEGFA-positive cells was found in subjects with the C allele (CC + CG genotypes) in comparison to the GG genotype (117 ± 35/mm² vs. 58 ± 21/mm²; p < 0.001). To conclude, the rs2010963 polymorphism is a potential genetic risk factor for myocardial infarction in Slovenian patients with T2DM.

Keywords: T2DM; VEGFA; atherosclerosis; myocardial infarction; polymorphism; rs2010963.

Figure 1

Immunohistochemical analysis of VEGFA protein expression relative to the rs2010963 genotypes. VEGFA-positive cells are stained brown; VEGFA-negative cells only have their nuclei stained blue. The blue arrows mark VEGFA-positive cells.