血管紧张素II受体基因多态性与原发性醛固酮增多症发病风险、亚型及预后的相关性研究

项目名称： 血管紧张素II受体基因多态性与原发性醛固酮增多症发病风险、亚型及预后的相关性研究

项目编号： No.81200578

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 吴准

作者单位： 厦门大学

项目金额： 23万元

中文摘要： 原发性醛固酮增多症（PA）是引起继发性高血压的最常见病因之一，PA患者占高血压人群比例已超过10%，遗传变异可能是PA发病的一个重要危险因素。我们前期研究发现，PA最主要的亚型- - 肾上腺醛固酮瘤（APA）与正常肾上腺组织相比，血管紧张素II-2型受体（AT2R）表达明显下调；此外，位于AT2R基因3'端非编码区的rs5194位点单核苷酸多态性（SNP）和APA发病危险相关联。ATR基因遗传变异可能会对该基因的表达、结构或者代谢活力产生影响，从而造成不同个体之间PA遗传易感性的差异。以上述发现为基础，本课题拟采用MGB-Taqman探针法检测ATR基因多个SNP位点在正常人群和PA人群中的基因型分布，通过病例对照研究进一步分析ATR基因多态性与PA的遗传易感性以及PA不同亚型的相关性，并通过病例随访研究探讨ATR基因多态性与PA临床预后的关系，为预测PA的发病危险和临床预后提供有用信息。

中文关键词： 血管紧张素Ⅱ1型受体；血管紧张素Ⅱ2型受体；单核苷酸多态性；原发性醛固酮增多症；

英文摘要： Primary aldosteronism (PA) is one of the most common form of secondary hypertension, with a prevalence of >10% among unselected hypertensives and 20% among patients with resistant hypertension. The most common clinical subtypes of PA are aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA), which respectively accounts for 60% and 30% of PA patients. However, the pathogenesis of PA and the causes of aldosterone hypersecretion remain unclear. The rennin-angiotensin system (RAS) mediates several classical physiological processes, including body water and electrolyte homeostasis, blood pressure regulation and aldosterone generation, based on the angiotensin Ⅱ type 1 and type 2 receptors (AT1R, AT2R) subtype system. Genetic or environmental factors may affect the expression and activity of AT1R and AT2R, which may impair their regulating functions and eventually lead to the development of diseases. Our previous research showed that rs5194 SNP at AT2R gene was significantly associated with the risk of APA .Further more,the mRNA or protein expression of AT2R in APA tissue is lower than that in normal adrenal gland tissues.On the basis of our previous study results, we aims to further investigate the associations of multi-polymorphisms in ATR genes with the risk , subtype and prognosis of PA.

英文关键词： AGTR1；AGTR2；SNP；primary aldosteronism；