Kangas-Kontio Tiia, Tapanainen Jari M, Huikuri Heikki, Savolainen Eeva-Riitta, Päivänsalo Markku, Kauma Heikki, Kesäniemi Y Antero, Savolainen Markku J, Kakko Sakari
Institute of Clinical Medicine, Department of Internal Medicine, Oulu University Hospital and Biocenter Oulu, Finland.
Scand J Clin Lab Invest. 2009;69(3):335-43. doi: 10.1080/00365510802607520.
Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor, but its role in atherogenesis is still unclear. Our goal was to study whether three variants of the VEGF gene, previously associated with VEGF production, are linked to atherosclerosis defined as carotid intima-media thickness (IMT) and as the risk of acute myocardial infarction (AMI).
Three VEGF gene single nucleotide polymorphisms (SNPs) (-2578A>C rs699947, -634C>G rs2010963 and +936C>T rs3025039) were genotyped in 516 control subjects of the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort and in 251 survivors of AMI. In the OPERA cohort, the genotyped SNPs were analysed for their association with IMT. The SNPs were also analysed for their association with the risk of AMI, a complication of advanced atherosclerosis. In addition, haplotype frequencies and their associated effects on IMT and on the risk of AMI were estimated.
None of the single genotyped polymorphisms was significantly associated with overall IMT or with the risk of AMI. However, the haplotype CCC was associated with higher overall IMT without plaques in women (p = 0.01, haplotypic effect +0.03 mm), the haplotype CCT with higher IMT without plaques in the internal carotid artery in men (p = 0.001, +0.11), while the haplotype AGT was associated with reduced AMI risk (p = 0.015, OR = 0.46).
Variation in the VEGF gene is weakly associated with IMT and the risk of AMI, but the effect can only be observed when the information of the SNPs is combined by constructing haplotypes.
血管内皮生长因子（VEGF）是一种强大的血管生成生长因子，但其在动脉粥样硬化发生中的作用仍不清楚。我们的目标是研究VEGF基因的三个先前与VEGF产生相关的变体是否与定义为颈动脉内膜中层厚度（IMT）以及急性心肌梗死（AMI）风险的动脉粥样硬化有关。
在OPERA（奥卢动脉粥样硬化风险研究项目）队列的516名对照受试者和251名AMI幸存者中，对三个VEGF基因单核苷酸多态性（SNP）（-2578A>C rs699947、-634C>G rs2010963和+936C>T rs3025039）进行基因分型。在OPERA队列中，分析基因分型的SNP与IMT的相关性。还分析了这些SNP与AMI风险（晚期动脉粥样硬化的一种并发症）的相关性。此外，估计了单倍型频率及其对IMT和AMI风险的相关影响。
单个基因分型的多态性均与总体IMT或AMI风险无显著相关性。然而，单倍型CCC与女性无斑块的总体IMT较高相关（p = 0.01，单倍型效应+0.03 mm），单倍型CCT与男性颈内动脉无斑块的IMT较高相关（p = 0.001，+0.11），而单倍型AGT与AMI风险降低相关（p = 0.015，OR = 0.46）。
VEGF基因的变异与IMT和AMI风险弱相关，但只有在通过构建单倍型组合SNP信息时才能观察到这种效应。
