【摘要】：目的采用病例對照研究方法，探討驗(yàn)證VEGFR-2基因啟動(dòng)子區(qū)多態(tài)性與動(dòng)脈粥樣硬化型缺血性腦卒中患病風(fēng)險(xiǎn)的相關(guān)性；探究VEGFR-2基因啟動(dòng)子區(qū)多態(tài)性與CISS分型中動(dòng)脈粥樣硬化型腦梗死各發(fā)病機(jī)制亞型的相關(guān)性。 方法根據(jù)病例對照研究方法收集病例150例，因血樣丟失或失訪等原因，最終腦梗死組入組103例，對照組入組43例。腦梗死組為CISS分型中動(dòng)脈粥樣硬化型缺血性卒中患者，根據(jù)其發(fā)病機(jī)制分為四個(gè)亞型組；對照組為無腦卒中癥狀或非腦卒中的輕癥患者。 抽取患者外周靜脈血，提取全血DNA；選取VEGFR-2基因啟動(dòng)子區(qū)-604T/C位點(diǎn)，利用PCR-酶切方法進(jìn)行基因分型。多元Logistic回歸模型校正傳統(tǒng)的心腦血管病危險(xiǎn)因素后，，分析基因啟動(dòng)子區(qū)多態(tài)性對缺血性腦卒中患病風(fēng)險(xiǎn)的相關(guān)性及發(fā)病機(jī)制各亞型組與其患病風(fēng)險(xiǎn)的的相關(guān)性。 結(jié)果腦梗死組VEGFR-2基因啟動(dòng)子區(qū)-604C等位基因頻率顯著低于對照組（腦梗死組9.7%，對照組45.3%，P0.0001），-604TC和CC基因型的頻率腦梗死組顯著低于對照組（腦梗死組TC12.6%、CC3.9%，對照組TC44.2%、CC23.3%，P0.0001）。亞組間分析發(fā)現(xiàn)各亞組間在基因型分布方面無明顯統(tǒng)計(jì)學(xué)意義（P0.05），腦梗死亞組動(dòng)脈-動(dòng)脈栓塞組、穿支動(dòng)脈閉塞組和混合型組的等位基因C的頻率低于對照組（P值均0.05），-604TC+CC的頻率也低于對照組（P值均0.05）。低灌注栓子清除功能下降組的等位基因頻率與-604TC+CC的基因型頻率雖低于對照組，但是用校正卡方檢驗(yàn)示P值均0.05；用多元Logistic回歸分析校正相關(guān)危險(xiǎn)性因素及保護(hù)性因素后，VEGFR-2基因啟動(dòng)子區(qū)-604C等位基因仍與降低缺血性腦卒中的患病風(fēng)險(xiǎn)相關(guān)。 結(jié)論VEGFR-2基因是動(dòng)脈粥樣硬化型缺血性腦卒中的易感基因；VEGFR-2型基因啟動(dòng)子區(qū)-604C等位基因與降低動(dòng)脈粥樣硬化型缺血性腦卒中的患病風(fēng)險(xiǎn)相關(guān)，尤其在CISS分型中動(dòng)脈-動(dòng)脈栓塞、穿支動(dòng)脈口閉塞及混合型亞型中表現(xiàn)比較明顯。
[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.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.3

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