The Genetic Study Of Patients With High Risk Of Sudden Cardiac Death

Objective The patients with high risk of sudden cardiac death can be divided into two groups. One is the patients with normal heart structure, another one is the patients with abnormal heart structure. The aim of this study is to search for the disease- causing gene and gene mutation of patients with Brugada type electrocardiogram (ECG) induced by fever (normal heart structure) and patients with lethal ventricular arrhythmia caused by coronary heart disease (abnormal heart structure),and reveal the genetic mechanism.Methods The DNA samples of patients with Brugada type ECG induced by fever and patients with lethal ventricular arrhythmia caused by coronary heart disease were collected. The candidate genes were screening by direct sequencing to see if the genetics was involved. ECG parameters (PR,QRS,QTc,TpTe,IRBBB) between two groups were compared using the statistical method and the risk was assessed.Results Study 1: Mutation was not found in 5 patients with fever-induced Brugada type ECG. None of patients died of sudden cardiac death in three years follow-up. 1 of 127 (0.8%) patients showed Brugada type ECG and 13 of 127(10.2%) showed incomplete right branch brand block (IRBBB). The QRS and TpTe are prolonger in fever group than in no-fever group. Study 2: 10 patients with lethal ventricular arrhythmia caused by coronary heart disease were collected. A missense mutation C→A, named A1446S was found in SCN5A at codon 1466, nucleotide 4388 in one patient, which was not found in the 100 normal control individuals.Conclusion 1. Fever-induced Brugada type ECGs in normal individuals were thought to be at very low risk for sudden cardiac death. The Chinese subjects with fever-induced Brugada type ECG might not be related to sodium channel mutation.2. We firstly found a novel SCN5A mutation which was related with VF caused by coronary heart disease in Chinese.