Homocysteine and MTHFR and VEGF gene polymorphisms: impact on coronary artery disease.
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.


CONCLUSIONS
Although there is an apparent association between VEGF C-2578A and the development of coronary atherosclerosis, this association is not independent of conventional cardiovascular risk factors.
Guerzoni
Alexandre Rodrigues
AR
Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.
Biselli
Patrícia Matos
PM
Godoy
Moacir Fernandes de
MF
Souza
Doroteia Rossi Silva
DR
Haddad
Renato
R
Eberlin
Marcos Nogueira
MN
Pavarino-Bertelli
Erika Cristina
EC
Goloni-Bertollo
Eny Maria
EM
D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics / Q000473:pathology; D004812:Epidemiologic Methods; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)