Early Repolarization Variant Incidence And SCN5A Gene Variants In General Population

Background:Early repolarization variants(ERV) is an electrocardiographic(ECG) phenomenon of cardiac repolarization abnormalities, originally thought to be a physiological ECG changes. Whereas, the mechanisms of this ECG changes tend to be similar to some diseases, such as acute myocardial ischemia, idiopathic ventricular fibrillation(IVF) and pathological Brugada syndrome. Therefore, some experts seem to have different views to its benign side. In recent years, with researchers’ continuous discoveries, ERV detection rate improves constantly. But the etiology and the pathogenesis of ERV have not been clearly defined, the current opinion is that it may be related to high vagal tone, cardiac repolarization variability and congenital genetic factors. Recently, studies have suggested that the pathogenesis of ERV may be associated with some certain cardiac ion channels( KCNJ8 、 CACNAl C 、CACNB2b 、 CACNA2D) genetic defects related, thinking that the potential arrhythmogenic of ERV may result from regulation defective of cardiac repolarization. The ion channels that can affect cardiac repolarization include sodium channel(SCN5A, SCN1b), potassium channel(IKr, IKs, IK- ATP, Ito) and calcium channels, in which the SCN5 A encoding sodium channel has a greater impact on early repolarization and should be drawn more concern. Currently, the correlations between ERV incidence in the population of our country and SCN5 A gene mutation has not been reported, so we may explore and discuss around this issue. Objective:To investigate the correlation between early repolarization variant incidence rate and cardiac sodium channel subunit α(SCN5A) gene variants in Chinese general population. Method:Collect ECG data and basic information of Nanchang Jiangxi distribute 751 subjects from Chinese adult normal ECG database from May – June, 2012. According to the J wave and J point elevation, and the distribution of different leads in ECG and different age groups, analyze the statistics of the incidence of early repolarization variants. Then using DNA direct sequencing technology, analyze the SCN5 A gene screening by detecting genetic variation genotype. Analyze the frequency and the leads when the J wave and J point elevation occur in the carrier of the mutated gene. Result:For general people above 18 year-old, the prevalence of ERV is 5.2%, and the incidence rate for male and female is 4.4 and 0.8 respectively,the rate of male versus female is 5.5:1. It is significantly far more away in male than in female(X2=37.95,P<0.005). The highest incidence rate occurs in the group over the 40-year-old, reaching 56.4%. In these 39 cases of ERV patients, the frequency of the J wave and the J point elevation is 64.1% and 35.9% respectively. In group which individual shows J wave, the V5 lead is the most common and obvious one. While in the group of J point elevation, the V4 lead shows the highest incidence. None of these ERV patients appears in AVR lead. The incidence of ERV occurs in left chest leads(V4、V5、V6) is the highest(76.90% in total cases), while in lateral leads(AVL) is the lowest(2.60% in total cases). Moreover,there is no correlation between the J wave or J point elevation amplitude whether >0.1mv or <0.1mv with age and gender. Among ERV patients, a novel SCN5 A gene heterozygosis missense mutation V1181 A was identified. This mutation is the nucleotide changed from T to C in the locus 3767 of SCN5 A gene, leading to the 1181 th amino acid of Nav1.5 protein change from valine to alanine. Conclusion:We firstly report that the incidence and the lead distribution in ECG of early repolarization variants in general people of our country, as well as the SCN5 A mutation is related to ERV and the V1181A-SCN5 A is a novel mutation.