VEGFR-2基因启动子区多态性与动脉粥样硬化型缺血性脑卒中易感相关性

发布时间：2019-04-26 07:27

【摘要】：目的采用病例对照研究方法，探讨验证VEGFR-2基因启动子区多态性与动脉粥样硬化型缺血性脑卒中患病风险的相关性；探究VEGFR-2基因启动子区多态性与CISS分型中动脉粥样硬化型脑梗死各发病机制亚型的相关性。方法根据病例对照研究方法收集病例150例，因血样丢失或失访等原因，最终脑梗死组入组103例，对照组入组43例。脑梗死组为CISS分型中动脉粥样硬化型缺血性卒中患者，根据其发病机制分为四个亚型组；对照组为无脑卒中症状或非脑卒中的轻症患者。抽取患者外周静脉血，提取全血DNA；选取VEGFR-2基因启动子区-604T/C位点，利用PCR-酶切方法进行基因分型。多元Logistic回归模型校正传统的心脑血管病危险因素后，，分析基因启动子区多态性对缺血性脑卒中患病风险的相关性及发病机制各亚型组与其患病风险的的相关性。结果脑梗死组VEGFR-2基因启动子区-604C等位基因频率显著低于对照组（脑梗死组9.7%，对照组45.3%，P0.0001），-604TC和CC基因型的频率脑梗死组显著低于对照组（脑梗死组TC12.6%、CC3.9%，对照组TC44.2%、CC23.3%，P0.0001）。亚组间分析发现各亚组间在基因型分布方面无明显统计学意义（P0.05），脑梗死亚组动脉-动脉栓塞组、穿支动脉闭塞组和混合型组的等位基因C的频率低于对照组（P值均0.05），-604TC+CC的频率也低于对照组（P值均0.05）。低灌注栓子清除功能下降组的等位基因频率与-604TC+CC的基因型频率虽低于对照组，但是用校正卡方检验示P值均0.05；用多元Logistic回归分析校正相关危险性因素及保护性因素后，VEGFR-2基因启动子区-604C等位基因仍与降低缺血性脑卒中的患病风险相关。结论VEGFR-2基因是动脉粥样硬化型缺血性脑卒中的易感基因；VEGFR-2型基因启动子区-604C等位基因与降低动脉粥样硬化型缺血性脑卒中的患病风险相关，尤其在CISS分型中动脉-动脉栓塞、穿支动脉口闭塞及混合型亚型中表现比较明显。
[Abstract]:Objective to investigate the relationship between VEGFR-2 gene promoter polymorphism and the risk of atherosclerotic ischemic stroke by a case-control study. To investigate the relationship between polymorphism of promoter region of VEGFR-2 gene and the pathogenesis subtypes of atherosclerotic cerebral infarction in CISS classification. Methods according to the method of case-control study, 150 cases of cerebral infarction were divided into two groups: 103 cases in the cerebral infarction group and 43 cases in the control group due to the loss of blood sample or the loss of follow-up. The cerebral infarction group was divided into four subtypes according to the pathogenesis of CISS classification of middle atherosclerotic ischemic stroke, and the control group was non-stroke symptom or non-stroke mild patients. The peripheral venous blood was extracted from the patients and the whole blood DNA; was extracted to select the 604T/C site of the promoter region of VEGFR-2 gene. PCR- digestion was used for genotyping. Multivariate Logistic regression model was used to analyze the relationship between gene promoter region polymorphism and the risk of ischemic stroke after correcting the traditional risk factors of cardio-cerebrovascular disease and the correlation between the pathogenesis of each subtype and the risk of ischemic stroke. Results the frequency of-604C allele in promoter region of VEGFR-2 gene in cerebral infarction group was significantly lower than that in control group (9.7% in cerebral infarction group, 45.3% in control group, P 0.0001). The frequencies of-604TC and CC genotypes in the cerebral infarction group were significantly lower than those in the control group (TC12.6%,CC3.9%, control group TC44.2%,CC23.3%,P0.0001 in the cerebral infarction group). Inter-subgroup analysis showed that there was no significant difference in genotype distribution among the subgroups (P0.05), and there was no significant difference in the distribution of genotypes between the subgroups of cerebral infarction (P05), the arterial-arterial embolization group in the cerebral infarction subgroup. The frequency of allele C in perforating artery occlusion group and mixed group was lower than that in control group (P0.05), and the frequency of-604TC CC was also lower than that in control group (P0.05). The allele frequency and the genotype frequency of-604TC CC in the low perfusion emboli clearance group were lower than those in the control group, but the corrected Chi-square test showed that the P values were 0.05; After adjusting the risk factors and protective factors by multivariate Logistic regression analysis, the-604C allele in the promoter region of the VEGFR-2 gene was still associated with the reduction of the risk of ischemic stroke. Conclusion VEGFR-2 gene is a susceptible gene of atherosclerotic ischemic stroke. The-604C allele in the promoter region of VEGFR- 2 gene is associated with reducing the risk of atherosclerotic ischemic stroke, especially in the CISS classification of middle artery-artery embolism, perforating artery orifice occlusion and mixed subtypes.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.3

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