家族聚集性脑缺血与脑出血差异表达易感基因的研究

发布时间：2018-06-20 02:49

本文选题：缺血性脑卒中 + 出血性脑卒中　；参考：《泰山医学院》2014年硕士论文

【摘要】：目的脑卒中是严重影响人类健康的疾病，其发病受遗传和外在环境等多因素的共同作用。大量流行病学调查显示:脑血管病发病呈现明显的家族聚集性，具有遗传倾向，且遗传因素对其发病的作用显著。为做好家族聚集性脑卒中的诊断和防治工作，，从基因角度研究家族性脑卒中的发病机制十分必要。本课题将家族聚集性的脑卒中病人按照卒中类型进行分类，利用全基因组分析(DNA chiP)技术，根据表达量的显著差异，筛选出与不同类型的家族聚集性脑卒中高度相关的基因，拟确定为脑卒中差异表达候选基因，在此基础上，使用实时定量PCR技术进一步验证差异表达，试图找出与家族聚集性脑卒中发病高度相关的易感基因，并分析这些易感基因的特征，以求成为家族性脑卒中个体化防治的有力理论依据。方法本实验两个病例组选自2012年12月至2013年12月在泰山医学院附属医院神经内科及外科住院的脑卒中病人，每个研究对象的家族内均有包括先症者在内2名以上的同类型脑卒中患者，包括10位均有缺血性脑卒中家族史(缺血性脑卒中人数超过该家族患者脑卒中总数的75%)的缺血性脑卒中患者，10位有出血性脑卒中家族史(出血性脑卒中人数超过该家族患者脑卒中总数的75%)的出血性脑卒中患者。另外选取6名同期在本院健康查体无脑血管病家族史的正常者作为对照组，对照组与实验组同民族，男女性别比例均衡，年龄相差不超过5岁，且在同一年龄组。病例组和对照组共26例。使用统一的调查表对选定家系的先证者以及其亲属进行调查，记录所有研究对象的一般临床资料，在征得所有受检对象同意后进行采样，采用DNA chiP技术，分别筛选出与缺血性脑卒中患者和出血性脑卒中患者高度相关的家族聚集性候选基因，在此结果的基础上，利用实时定量PCR技术进一步验证这些基因的差异表达。结果 1、脑出血组和脑缺血组在年龄、吸烟史、饮酒史、糖尿病病史、收缩压、舒张压、空腹血糖、血脂水平与对照组相比较，未见统计学差异(P＞0.05)。 2、RXRα基因的表达量在缺血性脑卒中组较正常对照组显著下调，且这种差异具有统计学意义； 3、EVL基因的表达量在缺血性脑卒中组较正常对照组显著上调，在出血性脑卒中组较正常对照组显著上调，且这种差异具有统计学意义； 4、SYK基因的表达量在缺血性脑卒中组较正常对照组显著下调，且这种差异具有统计学意义；在出血性脑卒中组变化不大； 5、LCK基因的表达量在缺血性脑卒中组较正常对照组显著下调，且这些差异具有统计学意义； 6、ID3基因的表达量在缺血性脑卒中组和出血性脑卒中组较正常对照组均显著上调，且这些差异具有统计学意义。结论 1、脑出血组和脑缺血组在年龄、吸烟史、饮酒史、糖尿病病史、收缩压、舒张压、空腹血糖、血脂水平与对照组相比较，未见统计学差异(P㧐0.05)。 2、RXRα基因可能与缺血性脑卒中的发病有关。缺失或低表达会增加缺血性脑卒中的易患性。 3、EVL基因可能与缺血性脑卒中和出血性脑卒中的发病均有关。其表达上调会增加脑卒中的易患性。 4、SYK基因可能与缺血性脑卒中的发病有关，但是具体的关系尚不清楚。 5、LCK基因可能与缺血性脑卒中的发病有关，低表达可能会增加缺血性脑卒中的易患性。 6、ID3基因与脑卒中的发病有关，高表达会增加缺血性与出血性脑卒中的易患性。ID3基因可能为缺血性与出血性脑卒中的易感基因。
[Abstract]:objective
Cerebral apoplexy is a disease which seriously affects human health. Its incidence is affected by many factors such as heredity and external environment. A large number of epidemiological investigations show that the incidence of cerebrovascular disease shows obvious familial aggregation, hereditary tendency, and the effect of hereditary factors on the disease. It is necessary to study the pathogenesis of familial apoplexy from a gene perspective. This topic classifies stroke patients with familial aggregation according to the type of stroke, and uses DNA chiP technology to screen out genes highly related to different types of familial aggregation of stroke according to the significant difference in expression. It is proposed to be a candidate gene for differential expression of stroke. On this basis, real time quantitative PCR technique is used to further verify the differential expression, trying to find the susceptible genes associated with familial aggregation of stroke, and analyze the characteristics of these susceptible genes in order to become a powerful theoretical basis for the individualized prevention and control of familial stroke.
Method
In this study, two cases of stroke patients were selected from December 2012 to December 2013 in the Department of Neurology and surgery in Affiliated Hospital of Tai'an Medical College. There were more than 2 stroke patients in each of the subjects including 10 of the family history of ischemic stroke (the number of ischemic stroke). 10 stroke patients with hemorrhagic stroke family history (bleeding cerebral apoplexy more than 75% of the total stroke in the family) were more than 75% of the total stroke in the family. In addition, 6 patients with normal cerebral vascular disease family history in our hospital were selected as the control group. In the control group and the experimental group, the sex ratio of men and women was balanced, the difference of age was not more than 5 years old, and in the same age group, 26 cases in the case group and the control group. A unified questionnaire was used to investigate the selected family members and their relatives, to record the general clinical data of all the subjects, and to obtain the consent of all the subjects. DNA chiP technique was used to screen out the family clustered candidate genes highly related to patients with ischemic stroke and hemorrhagic stroke. On the basis of the results, the differential expression of these genes was further verified by real-time quantitative PCR technique.
Result
1, there was no statistically significant difference in age, smoking history, drinking history, diabetes history, systolic pressure, diastolic pressure, fasting blood pressure, fasting blood glucose and blood lipid level compared with the control group (P > 0.05).
2, the expression of RXR alpha gene was significantly lower in the ischemic stroke group than in the normal control group, and the difference was statistically significant.
3, the expression of EVL gene was significantly up-regulated in the ischemic stroke group than in the normal control group, and the difference was significantly higher in the hemorrhagic stroke group than in the normal control group, and the difference was statistically significant.
4, the expression of SYK gene was significantly lower in the ischemic stroke group than in the normal control group, and the difference was statistically significant, and there was no significant change in the hemorrhagic stroke group.
5, the expression of LCK gene in ischemic stroke group was significantly lower than that in normal control group, and these differences were statistically significant.
6, the expression of ID3 gene in ischemic stroke group and hemorrhagic stroke group was significantly higher than that in normal control group, and these differences were statistically significant.
1, there was no statistically significant difference in age, smoking history, drinking history, diabetes history, systolic pressure, diastolic pressure, fasting blood pressure, fasting blood glucose and blood lipid level compared with the control group (P? 0.05).
2, RXR alpha gene may be associated with ischemic stroke. Loss or low expression will increase the susceptibility of ischemic stroke.
3, the EVL gene may be associated with the onset of ischemic stroke and hemorrhagic stroke.
4, the SYK gene may be related to the pathogenesis of ischemic stroke, but the specific relationship is not yet clear.
5, the LCK gene may be associated with ischemic stroke, and low expression may increase the risk of ischemic stroke.
6, the ID3 gene is associated with the onset of stroke. High expression may increase the susceptibility of ischemic and hemorrhagic stroke to susceptible.ID3 genes, which may be susceptible genes for ischemic and hemorrhagic 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

【参考文献】