Biselli Patrícia Matos, Guerzoni Alexandre Rodrigues, de Godoy Moacir Fernandes, Pavarino-Bertelli Erika Cristina, Goloni-Bertollo Eny Maria
Genetics and Molecular Biology Research Unit, Unidade de Pesquisa em Genética e Biologia Molecular-UPGEM, São José do Rio Preto Medical School, Av. Brigadeiro Faria Lima No 5416, Bloco U-6, Famerp, 15.090-000 SP, Brazil.
Heart Vessels. 2008 Nov;23(6):371-5. doi: 10.1007/s00380-008-1057-6. Epub 2008 Nov 27.
Atherosclerosis results from a complex interaction between environment and genetic risk factors. The gene encoding vascular endothelial growth factor (VEGF) is associated with differential protein expression and has been investigated in coronary artery disease (CAD) studies. Based on this, we aimed at determining if patients with CAD are affected by polymorphisms (-2 578, -1 154, and 936) in the VEGF gene, and also if these polymorphisms are associated with the number of diseased vessels and degree of arterial obstruction. The case group was formed by 175 Caucasian patients with angiographically confirmed CAD, and the control group involved 108 Caucasian patients with normal coronary angiograms. Polymerase chain reaction (PCR) was used for genotyping. Allele frequencies for VEGF -2 578A, -1 154A, and 936T were 0.46, 0.38, and 0.14 in cases and 0.49, 0.30, and 0.13 in control subjects. Allele and genotype distribution did not significantly differ between groups. A higher frequency of the VEGF -2 578AA genotype was observed in the group with three vessel disease (P = 0.008). No association between the VEGF -2 578, -1 154, and 936 polymorphisms and degree of arterial obstruction was observed. The frequency of carriers of two copies of the haplotype AG (-2 578/-1 154) were higher in the group with three-vessel disease (P = 0.05). In summary, our report shows that the VEGF -2 578 polymorphism has an influence on CAD severity, possibly because of a reduced VEGF expression, suggesting a protective effect of VEGF in atherosclerosis.
动脉粥样硬化是环境和遗传风险因素之间复杂相互作用的结果。编码血管内皮生长因子(VEGF)的基因与蛋白质表达差异相关,并且已经在冠状动脉疾病(CAD)研究中进行了调查。基于此,我们旨在确定CAD患者是否受VEGF基因多态性(-2578、-1154和936)的影响,以及这些多态性是否与病变血管数量和动脉阻塞程度相关。病例组由175例经血管造影证实患有CAD的白种人患者组成,对照组包括108例冠状动脉造影正常的白种人患者。采用聚合酶链反应(PCR)进行基因分型。VEGF -2578A、-1154A和936T的等位基因频率在病例组中分别为0.46、0.38和0.14,在对照组中分别为0.49、0.30和0.13。两组之间的等位基因和基因型分布没有显著差异。在三支血管病变组中观察到VEGF -2578AA基因型的频率较高(P = 0.008)。未观察到VEGF -2578、-1154和936多态性与动脉阻塞程度之间的关联。单倍型AG(-2578 / -1154)两个拷贝携带者的频率在三支血管病变组中较高(P = 0.05)。总之,我们的报告表明,VEGF -2578多态性对CAD严重程度有影响,可能是由于VEGF表达降低,提示VEGF在动脉粥样硬化中具有保护作用。