ALDH2基因多态性与脑卒中易感性的关系

发布时间：2018-02-01 19:10

本文关键词： ALDH2 基因多态性脑卒中易感性　出处：《泰山医学院》2014年硕士论文　论文类型：学位论文

【摘要】：目的测定ALDH2基因多态性，研究ALDH2各基因型在健康体检者和脑卒中患者中的分布差异，以及在脑卒中各临床分型中的分布情况，明确ALDH2对脑卒中发病的意义，为脑卒中的预防提供依据。方法收集所有研究对象血样，包括健康体检者148例（男68例，女80例），入院确诊的脑卒中患者154例（脑梗死116例，脑出血38例）。采用实验室方法和DNA微阵列芯片法进行ALDH2基因Glu504Lys多态性检测，以上两种方法均经96通道毛细管电泳的高通量基因测序方法进行验证。对所有研究对象记录性别、年龄、籍贯、吸烟及饮酒史，有无高血压、糖尿病、冠心病等既往病史以及颈动脉易损斑块的有无、类型等基本临床资料。用χ2检验比较各实验组基因分布与对照组基因分布差异的显著性意义，用logistic回归分析确定ALDH2基因在脑卒中发病中的意义。结果 1.成功建立了实验室检测ALDH2基因Glu504Lys多态性的方法，为大样本检测ALDH2基因多态性提供了可能，且方法经基因测序验证，，结果准确、可靠。 2.统计分析显示，ALDH2基因Glu504Lys多态性分布符合Hardy-Weinberg遗传平衡。 3.经χ2检验，ALDH2基因型及等位基因G、A在脑卒中组和正常组中分布具有显著性的统计学差异（P0.05），ALDH2基因多态性是脑卒中发生的危险因素。 4.经χ2检验，ALDH2基因型及等位基因G、A在脑梗死组与脑出血组之间分布具有显著性差异，脑梗死组基因型及等位基因A分布比例大于正常组（P0.05），脑梗死可能与ALDH2基因突变以及等位基因A有关。 5.经单因素logistic回归分析结果显示ALDH2基因多态性（P=0.036，OR=2.318）、饮酒、高血压、糖尿病、冠心病以及性别均为脑卒中发生的危险因素，进一步经多因素Logistic回归分析结果显示年龄（OR=0.947）、吸烟（OR=1.816）、饮酒（OR=5.828）、高血压（OR=2.230）、糖尿病（OR=8.017）、冠心病（OR=4.524）是脑卒中发生的独立危险因素，而ALDH2基因多态性对脑卒中的影响不如其他危险因素明显（P=0.849，OR=1.094），不能确定ALDH2基因多态性是脑卒中发生的独立危险因素。 6.做颈动脉超声检查的66例脑梗死患者中有75.76%（50例）出现动脉粥样硬化斑块，有46.97%（30例）出现易损斑块，占出现动脉粥样硬化斑块的60%。经χ2检验，脑梗死的发生与动脉粥样硬化斑块的形成有关（P0.05），且形成斑块类型以易损斑块为主。结论 1.泰安地区人口中存在ALDH2基因Glu504Lys多态性。 2.脑血栓形成和脑栓塞组ALDH2等位基因A的分布明显高于正常人群。等位基因A是脑梗死的危险因素。 3. ALDH2基因多态性对脑卒中的影响不如高血压、糖尿病、冠心病、吸烟、饮酒、年龄等因素显著，不能确定ALDH2基因多态性是否是脑卒中发生的独立危险因素。
[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.
【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.3

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