国人冠心病发生VTVF的首个致病基因SCN5A的发现及突变功.pptVIP

国人冠心病发生VT/VF的首个致病基因SCN5A的发现及突变功能分析 胡金柱 南昌大学第二附属医院心内科 VT/VF Caused by Coronary Heart Disease in Chinese Patients:the First Disease-Causing Gene SCN5A and Function Analysis of Mutations Outline Background Materials and Methods Discussion Conclusions Incidence of SCD (Yearly) More than 3 million in the world 300,000-400,000 in U.S ? in China 50万 Non- Inherited Inherited Long QT Syndrome Short QT syndrome Sudden cardiac death Structurally Nomal Heart Structurally abnomal Heart Coronary heart disease Brugada Syndrome CPVT · · · · · · HCM · · · · · · 60-80% SCD 80-90% VT/VF Disease-causing gene of CHD MEF2A LRP6 Wang L et al. Science; 2003 Arya Mani et al. Science; 2007 Background CHD SCD Only one disease-causing gene SCN5A HU et al;Heart Rhythm;2007 In China Genetics ? Background Candidate gene Molecule genetic technic Cell patch clamp Molecular biology Disease-causing gene Cell electrophysiologic mechanism 31 patients (with VF caused by CHD) 2 patients with SCN5A mutations Results R812C(精氨酸812半胱氨酸) I1469S(异亮氨酸1469丝氨酸) Results SCN5A mutation: R812C Normal control SCN5A mutation:I1469S Normal control Age: Sex: Symptom: Arrest: CAG： UCG: Dignosis: Age: Sex： Symptom： Arrest： CAG: UCG: Dignosis： Patient 1 Patient 2 62 year old male intermittent dyspnea and chest pain half month,syncope once yes LAD 80%,RCA 95% stenosis LVEF 78%,LVEDD 43mm,LV diastolic dysfunction CHD,ACS, VF,NYHA I 70 year old male chest pain 3 days,dyspnea 1 day yes LCX 80%,LAD 80-90% stenosis,OM and RCA occlusion LVEF 37%,LVEDD 44mm,LV segmental wall abnormal motion CHD,AMI,VF,NYHA Ⅳ, pulmonary infection,2-DM Results SCD VT/VF Coronary vascular events Autonomic tone change Myocardial injury Metabolic conditions Ionic state of myocardium CHD Discussion Cardiac electric activity abnormal Lethral arrhythmia caused by CHD Ionic channel function abnormal Gene mutation importan