LTA4H基因多态性对动脉粥样硬化型脑梗死的影响

发布时间：2018-05-24 02:46

本文选题：缺血性脑卒中 + 白三烯A4水解酶　；参考：《青岛大学》2014年硕士论文

【摘要】：脑卒中是一种严重威胁人类生命健康的常见的神经系统疾病,缺血性脑卒中的发病除与传统的危险因素如高血糖、高血压、高血脂、吸烟等相关以外,遗传变异也是其重要的发病原因,环境与遗传因素可单独对缺血性脑卒中作用外,也可通过两者的相互作用增加易感性。作为白三烯生成过程中一个重要限速酶的白三烯A4水解酶(LTA4),许多对其基因多态性的研究多集中在癌症及呼吸系统疾病,很少有研究探讨其与缺血性脑卒中的关系,本研究旨在以LTA4H作为候选基因,探讨其基因多态性对动脉粥样硬化型缺血性脑卒中的影响,为该病的个体预防及治疗提供临床资料。研究目的：探讨白三烯A4水解酶基因多态性对动脉粥样硬化型梗死发病率的影响。研究方法：本实验采用病例对照研究和分子流行病学研究方法,选择山东地区人群为研究对象,病例组为2010年9月到2012年10期间于月青岛大学医学院附属医院住院的动脉粥样硬化型脑梗死患者450例,本实验纳入病例经临床、MRA及颈部血管超声或头颈部CTA或全脑血管造影DSA检查均符合全国第四届脑血管病会议修订的脑血管病诊断标准及1993年由美国Adams等制订的TOAST(the trial of or910172in acute stroke treatment)分型标准。对照组来自同期本科室及其他科室、健康体检中心的性格、年龄相匹配的非缺血性脑卒中者400例,应用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)方法,检测LTA4H基因rs6538697位点的基因多态性并行结果分析。研究结果：病例组和对照组LTA4Hrs6538697T/C位点基因型分布差异具有统计学意义(X2＝4.49,P0.05)。病例组C等位基因频率显著高于对照组,T等位基因频率明显低于对照组,差异有统计学意义(X2＝7.27,P0.05),,经logistic回归方法排除脑卒中的传统危险因素如高血压、糖尿病、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)影响后,LTA4Hrs6538697C等位基因携带者动脉粥样硬化型脑梗死易感性增高1.34倍(OR=1.34,95%CI1.010-1.786, P0.05)。结论：LTA4Hrs6538697C/T基因多态性与山东地区人群动脉粥样硬化型脑梗死具有相关性,rs6538697T-C等位基因突变能增加动脉粥样硬化型脑梗死的发病风险。
[Abstract]:Stroke is a common nervous system disease that seriously threatens human life and health. The incidence of ischemic stroke is related to traditional risk factors such as hyperglycemia, hypertension, hyperlipidemia, smoking and so on. Genetic variation is also an important cause of ischemic stroke. Environmental and genetic factors can not only play a role in ischemic stroke, but also increase susceptibility through the interaction of the two factors. As an important rate-limiting enzyme in the formation of leukotriene, leukotriene A4 hydrolase LTA4 has been studied mostly in cancer and respiratory diseases. The purpose of this study was to investigate the effect of LTA4H gene polymorphism on atherosclerotic ischemic stroke, and to provide clinical data for individual prevention and treatment of Atherosclerotic stroke. Objective: to investigate the effect of leukotriene A 4 hydrolase gene polymorphism on the incidence of atherosclerotic infarction. Methods: a case-control study and a molecular epidemiology study were conducted to study the population in Shandong province. The case group consisted of 450 patients with atherosclerotic cerebral infarction hospitalized in the affiliated Hospital of Medical College of Qingdao University from September 2010 to October 2012. The clinical MRA, cervical vascular ultrasound, head and neck CTA or DSA examination were in accordance with the revised diagnostic criteria of cerebrovascular disease and TOAST(the developed by Adams et al in 1993. Trial of or910172in acute stroke treatment) typing standard. In the control group, 400 patients with non-ischemic stroke were collected from our department and other departments and health examination centers in the same period. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used. The gene polymorphism of rs6538697 locus of LTA4H gene was analyzed by parallel analysis. Results: the difference of genotype distribution of LTA4Hrs6538697T/C locus between case group and control group was statistically significant. The frequency of C allele in the case group was significantly higher than that in the control group, and the frequency of T allele was significantly lower than that in the control group. The difference was statistically significant. The traditional risk factors of stroke such as hypertension and diabetes were excluded by logistic regression. The susceptibility to atherosclerotic cerebral infarction was 1.34 times higher in patients with TGG, TC, LDL-C, LTA4Hrs6538697C alleles, and 1.34-95 CI 1.010-1.786, P 0.055.The results showed that there was no significant difference between LTA4Hrs6538697C allele carriers and patients with atherosclerotic cerebral infarction (LTA4Hrs6538697C). Conclusion the allele mutation of rs6538697T-C allele may increase the risk of atherosclerotic cerebral infarction in Shandong area.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.3

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