TGF-β1基因单核苷酸多态性在心房颤动发生和预后中的作用

项目名称： TGF-β1基因单核苷酸多态性在心房颤动发生和预后中的作用

项目编号： No.81200133

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 曹海龙

作者单位： 南京大学

项目金额： 23万元

中文摘要： 心房颤动是临床上最常见的心律失常，发病率逐年增加。它可诱发和加重心力衰竭，增加血栓栓塞的发生率，已成为威胁公众健康的重要致死、致残因素。房颤最重要的病理基础就是心房间质纤维化，而TGF-β1在其中起着重要作用。但由于其准确的调节机制尚不清，因而限制了其作为"上游治疗"在临床中的应用。本课题紧密结合临床，应用分子流行病学技术探讨TGF-β1基因多态性在非瓣膜病房颤的发生和消融后复发中的作用，并进一步在离体与在体功能学水平揭示其中精确的作用机制。为基于调节TGF-β1的房颤"上游治疗"奠定一定的理论基础和提供有效的干预靶点。此外，通过筛选包括TGF-β1基因多态性在内的临床指标用于术前判断行消融治疗患者的预后，从而进一步充实射频消融术的适应症，并为消融治疗术后其他相关辅助干预提供询证医学依据。

中文关键词： TGF-β1；多态性；心房颤动；发生；预后

英文摘要： Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. The incidence is increasing these years. It can induce and aggravate heart failure and increase the risk of thromboembolism. Thus, it has been one of the most important threatens to public health. The key pathological substrate of AF is atrial interstitial fibrosis, in which transforming growth factor-beta 1 (TGF-β1) plays a vital role. However, because the precise regulatory mechanisms remain largely unknown, its clinical utilization as one of "Upstream treatments" is limited. In this study, it was designed to investigate the association between single nucleotide polymorphisms of TGF-β1 gene and development and prognosis of non-valvular AF in a large hospital-based case-control population. Furthermore, the potential functional effects of these polymorphisms will be verified both in vivo and vitro. Therefore, the results will strengthen the theoretical foundation and provide new therapeutic targets by regulating TGF-β1 for AF "Upstream treatments". In addition, screening clinical markers including TGF-β1 gene polymorphisms which can preoperatively predict the prognosis of AF patients after ablation will enrich the indications for AF ablation, and provide the evidence for selecting relevant adjunctive therapies after AF ablat

英文关键词： TGF-β1；Polymorphisms；Atrial fibrillation；Development；Prognosis