本文關(guān)鍵詞： ALDH2 基因多態(tài)性 腦卒中 易感性　出處：《泰山醫(yī)學院》2014年碩士論文　論文類型：學位論文

【摘要】：目的 測定ALDH2基因多態(tài)性，研究ALDH2各基因型在健康體檢者和腦卒中患者中的分布差異，以及在腦卒中各臨床分型中的分布情況，明確ALDH2對腦卒中發(fā)病的意義，為腦卒中的預防提供依據(jù)。 方法 收集所有研究對象血樣，包括健康體檢者148例（男68例，女80例），入院確診的腦卒中患者154例（腦梗死116例，腦出血38例）。采用實驗室方法和DNA微陣列芯片法進行ALDH2基因Glu504Lys多態(tài)性檢測，以上兩種方法均經(jīng)96通道毛細管電泳的高通量基因測序方法進行驗證。對所有研究對象記錄性別、年齡、籍貫、吸煙及飲酒史，有無高血壓、糖尿病、冠心病等既往病史以及頸動脈易損斑塊的有無、類型等基本臨床資料。用χ2檢驗比較各實驗組基因分布與對照組基因分布差異的顯著性意義，用logistic回歸分析確定ALDH2基因在腦卒中發(fā)病中的意義。 結(jié)果 1.成功建立了實驗室檢測ALDH2基因Glu504Lys多態(tài)性的方法，為大樣本檢測ALDH2基因多態(tài)性提供了可能，且方法經(jīng)基因測序驗證，，結(jié)果準確、可靠。 2.統(tǒng)計分析顯示，ALDH2基因Glu504Lys多態(tài)性分布符合Hardy-Weinberg遺傳平衡。 3.經(jīng)χ2檢驗，ALDH2基因型及等位基因G、A在腦卒中組和正常組中分布具有顯著性的統(tǒng)計學差異（P0.05），ALDH2基因多態(tài)性是腦卒中發(fā)生的危險因素。 4.經(jīng)χ2檢驗，ALDH2基因型及等位基因G、A在腦梗死組與腦出血組之間分布具有顯著性差異，腦梗死組基因型及等位基因A分布比例大于正常組（P0.05），腦梗死可能與ALDH2基因突變以及等位基因A有關(guān)。 5.經(jīng)單因素logistic回歸分析結(jié)果顯示ALDH2基因多態(tài)性（P=0.036，OR=2.318）、飲酒、高血壓、糖尿病、冠心病以及性別均為腦卒中發(fā)生的危險因素，進一步經(jīng)多因素Logistic回歸分析結(jié)果顯示年齡（OR=0.947）、吸煙（OR=1.816）、飲酒（OR=5.828）、高血壓（OR=2.230）、糖尿�。∣R=8.017）、冠心�。∣R=4.524）是腦卒中發(fā)生的獨立危險因素，而ALDH2基因多態(tài)性對腦卒中的影響不如其他危險因素明顯（P=0.849，OR=1.094），不能確定ALDH2基因多態(tài)性是腦卒中發(fā)生的獨立危險因素。 6.做頸動脈超聲檢查的66例腦梗死患者中有75.76%（50例）出現(xiàn)動脈粥樣硬化斑塊，有46.97%（30例）出現(xiàn)易損斑塊，占出現(xiàn)動脈粥樣硬化斑塊的60%。經(jīng)χ2檢驗，腦梗死的發(fā)生與動脈粥樣硬化斑塊的形成有關(guān)（P0.05），且形成斑塊類型以易損斑塊為主。 結(jié)論 1.泰安地區(qū)人口中存在ALDH2基因Glu504Lys多態(tài)性。 2.腦血栓形成和腦栓塞組ALDH2等位基因A的分布明顯高于正常人群。等位基因A是腦梗死的危險因素。 3. ALDH2基因多態(tài)性對腦卒中的影響不如高血壓、糖尿病、冠心病、吸煙、飲酒、年齡等因素顯著，不能確定ALDH2基因多態(tài)性是否是腦卒中發(fā)生的獨立危險因素。
[Abstract]:Purpose To determine the polymorphism of ALDH2 gene and to study the distribution of ALDH2 genotypes in healthy persons and stroke patients, and to study the distribution of ALDH2 genotypes in each clinical type of stroke. To clarify the significance of ALDH2 in the pathogenesis of stroke and to provide evidence for the prevention of stroke. Method Blood samples were collected from all subjects, including 148 healthy persons (68 males and 80 females) and 154 stroke patients (116 patients with cerebral infarction). The Glu504Lys polymorphism of ALDH2 gene was detected by laboratory method and DNA microarray method in 38 patients with intracerebral hemorrhage. The above two methods were verified by high throughput gene sequencing method using 96 channel capillary electrophoresis. Sex, age, origin, smoking and drinking history, hypertension and diabetes were recorded in all subjects. The basic clinical data such as coronary heart disease (CHD) history and carotid plaque types were compared by 蠂 2 test. The difference of gene distribution between the experimental group and the control group was significant. Logistic regression analysis was used to determine the significance of ALDH2 gene in stroke. Results 1. The method of detecting Glu504Lys polymorphism of ALDH2 gene in laboratory was established successfully, which provided the possibility for large sample to detect the polymorphism of ALDH2 gene, and the method was verified by gene sequencing. The results are accurate and reliable. 2. Statistical analysis showed that the Glu504Lys polymorphism distribution of ALDH2 gene was consistent with the Hardy-Weinberg genetic balance. 3. The distribution of ALDH2 genotype and allele GMA was significantly different between stroke group and normal group by 蠂 2 test (P 0.05). ALDH2 gene polymorphism is a risk factor for stroke. (4) the distribution of ALDH2 genotype and allele GFAA was significantly different between cerebral infarction group and cerebral hemorrhage group by 蠂 2 test. The distribution of genotype and allele A in cerebral infarction group was higher than that in normal group (P0.05A). Cerebral infarction may be related to ALDH2 gene mutation and allele A. 5. Univariate logistic regression analysis showed that the polymorphism of ALDH2 gene was 0.036, drinking alcohol, hypertension, diabetes mellitus. Coronary heart disease and sex were the risk factors of stroke. The results of multivariate Logistic regression analysis showed that age was 0.947 and smoking was 1.816). The risk factors of stroke were drinking alcohol 5.828, hypertension 2.230, diabetes 8.017, coronary heart disease 4.524). However, the effect of ALDH2 gene polymorphism on stroke was not as significant as that of other risk factors, P0. 849 and OR1. 094). It is not certain that ALDH2 gene polymorphism is an independent risk factor for stroke. 6.Among 66 patients with cerebral infarction examined by carotid ultrasound, there were 75.76and 50) atherosclerotic plaques and 46.97um) vulnerable plaques. By 蠂 2 test, the occurrence of cerebral infarction was related to the formation of atherosclerotic plaque, and the type of plaque formation was mainly vulnerable plaque. Conclusion 1. ALDH2 gene Glu504Lys polymorphism exists in Tai'an population. 2. The distribution of ALDH2 allele A in patients with cerebral thrombosis and cerebral embolism was significantly higher than that in normal controls, and allele A was the risk factor of cerebral infarction. 3.The effect of ALDH2 gene polymorphism on stroke was less significant than that on hypertension, diabetes, coronary heart disease, smoking, drinking, age and so on. It is not certain whether ALDH2 gene polymorphism is an independent risk factor for stroke.
【學位授予單位】：泰山醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R743.3

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