fkbp12.6与肥厚性心肌病的分子遗传学分析 word格式.docxVIP

ABSTRACTBackground and Objective:Hypertrophic Cardiomyopathy(HCM) is one primary myocardiopathy characterized by unexplained left ventricle with or not right ventricle asymmetrical hypertrophy, often involving ventricular septum, which is a major cause of sudden cardiac death among adolescents and athletes. The majority of HCM show familial aggregation, which is considered to be a single gene mutation of autosomal dominant inheritance disease. Due to most of pathogenic genes encode sarcomere proteins, HCM was also considered to be a sarcomeric disease.Recent studies have found that these genes are the causative gene of HCM, such as PLN, JPH2, RyR2, CASQ2,which code proteins involved in calcium transport. It has been proved that abnormal intracellular calcium overload involves in the process of the occurrence and development of cardiac hypertrophy, FK506 binding protein 12.6(FKBP12.6) is one of regulatory proteins of cardiac sarcoplasmic reticulum ryanodine receptor 2 (Ryanodine Receptor 2, RyR2), which plays an important role in the maintenance of intracellular calcium homeostasis. Recently researches showed that FKBP12.6 gene knockout mices displayed that the weight of mice heart,the thickness of left ventricular wall and ventricular septum increased significantly, which was similar to HCM. Based on above viewpoints, our study aims to explore whether the FKBP12.6 is the causative gene of HCM, further more to provide new sight for HCM in molecular genetics research, clinical diagnosis and treatment.Method:In reference to Chinese experts consensus in 2007 ,American Cardiology Foundation / America Heart Association (ACCF/AHA) in 2011 and European Society of Cardiology(ESC) issued guidelines for the diagnosis and management of hypertrophic cardiomyopathy. The study was approved by hospital ethics committee and all subjects were gave a written informed consent , we enrolled in Thirty sevenHCM patients and collected the clinical data and peripheral venous blood (2-5mL).