Summary

Background: Polymorphisms in genes involved in the atherosclerosis development, angiogenesis, and homocysteine (Hcy) metabolism could be risk factors for coronary artery disease (CAD). Objective: To evaluate the effect of the VEGF C-2578A and MTHFR C677T polymorphisms on CAD, and the association of these polymorphisms with the severity and extension of atherosclerotic lesions and Hcy concentrations. Methods: Two hundred and forty-four subjects were evaluated by coronary angiography and included in the study (145 with CAD and 99 controls). The VEGF C-2578A and MTHFR C677T polymorphisms were investigated by the PCR-SSCP and PCR-RFLP techniques, respectively. Plasma Hcy was quantified by liquid chromatography/sequential mass spectrometry (LC-MS/MS). Results: There was no significant difference in allele and genotype distribution between the groups, for both polymorphisms. The univariate analysis showed a higher frequency of the VEGF-2578AA genotype in the group with three-vessel disease (p=0.044). In addition, the VEGF-2578CA genotype was observed more frequently among individuals with <95 % stenosis (p=0.010). After adjustment for other risk factors for CAD in a multivariate model, the VEGF C-2578A polymorphism was not found to be an independent correlate of CAD (p=0.688). The MTHFR polymorphism did not show any association with the extension and/or severity of the CAD. The MTHFR C677T polymorphism showed no direct association with hyperhomocysteinemia or increased mean plasma concentrations of Hcy