缓激肽β_2受体、内皮型一氧化氮合酶、G蛋白β_3亚单位基因多态性与ACEI降压疗效相关性研究
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  • 英文题名:The Relationship between the -58T/C Polymorphism of the Bradykinin β_2 Receptor Gene, the G894T Polymorphism of the Endothelial Nitric Oxide Synthase, the C825T Polymorphism of G Protein β_3 Subunit and Antihypertensive Response to ACE Inhibitor
  • 作者:陈改玲
  • 论文级别:博士
  • 学科专业名称:心血管内科学
  • 学位年度:2004
  • 导师:刘国仗 ; 党爱民 ; 吴海英
  • 学科代码:100201
  • 学位授予单位:中国协和医科大学
  • 论文提交日期:2004-05-01
摘要
原发性高血压是多因素疾病,它是冠心病、脑卒中、左室肥厚、急性心肌梗死等心血管疾病的独立危险因素。目前有研究表明,仅有50%的高血压患者能受益于抗高血压的治疗,不同个体对同一降压药物的反应性存在着明显差异,其影响因素很多,其中遗传因素可能与个体之间降压疗效的差异相关。筛选降压疗效相关基因的研究,对于临床中避免使用无效或低效的抗高血压药物,从而改善目前低控制率现状有重要的意义。
     肾素血管紧张素系统(RAS)与激肽释放酶-激肽系统(KKS)是体内参与血压调节的两个重要系统。ACEI主要通过干预RAS及KKS而发挥其降压作用。RAS基因多态性与ACEI降压疗效研究较多,而KKS与ACEI降压疗效相关性研究尚未见报道。近年缓激肽β_2受体(BDKRB2)、内皮型一氧化氮合酶(eNOS)、G蛋白β_3亚单位(GNB3)在血压调节中的作用备受重视。本研究探讨我国汉族原发性高血压患者BDKRB2基因启动子区-58T/C多态性、eNOS基因第7外显子的G894T多态性、GNB3基因第10外显子C825T多态性分布及其与ACEI降压疗效的相关性。
     研究对象与方法:本研究对象来源于国内多中心的临床试验,选择1-2级原发性高血压患者(诊断标准参照1999年中国高血压防治指南标准),经安慰剂治疗2周后,分别给予咪达普利5mg/日或贝那普利10mg/日。治疗3周后,如果坐位DBP≥90mmHg,则剂量加倍,继续治疗3周,第6周末观察降压疗效。采用聚合酶链反应(PCR)分
Essential hypertension is a kind of multiple genetic disease,which is the independent risk factors of coronary heart disease, stroke, left ventricular hypertrophy, acute myocardial infarction. Several studies showed only 50% of the patients benefit from antihypertensive drugs. Individuals may respond differently to the same antihypertensive medication. It has been suspected that interindividual variation on the efficacy may be influenced by genetic factors. It is an useful strategy to stduy candidate genes of antihypertensive drugs efficacy.
    It is well known that bradykinin β_2 receptor,G protein β_3 subunit, endothelial nitric oxide synthase play the important role in blood pressure regulation.The aim of present study is to investigate the — 58T/C polymorphism of the bradykinin β_2 receptor gene (BDKRB2) , the G894T polymorphism of the endothelial nitric oxide synthase (eNOS) and the C825T polymorphism of G protein β_3 subunit in Chinese essential hypertensive patients and the relationship between genotype and antihypertensive response to ACE inhibitor.
引文
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