Study On The Molecular Genetic Correlation Between Atiral Fibrillation And Sodium Channel Gene SCN5A

Background：Atrial fibrillation is the most common arrhythmia among adults. It is anarrhythmia with high mortality and disability rate which is loss of regular atrialelectrical activity, replaced by fast-disordered fibrillation waves (f wave). It can leadto ventricular rhythm disorders, impaired heart function and atrial mural thrombosis.Atrial fibrillation has been currently considered as the result of the interaction onvarious mechanisms and factors, and it can lead to electrical and structuralremodeling in atrium. Recent studies have shown that gene variations of ion channels,the gap junction proteins, and nuclear pore proteins are closely associated with atrialfibrillation. Sodium channel gene SCN5A is one of the virulence genes, but there isno such research between atrial fibrillation and SCN5A gene in Chinese populationyet.Objective：To explore the molecular genetic relevance between SCN5A and atrialfibrillation in Chinese population.Method：1. According to the diagnostic criteria of atrial fibrillation guideline, wecollected the clinical datum and blood samples of patients with atrial fibrillation inour hospital. All selected patients did routine examinations and echocardiography, andwe detailedly estimated their cardiovascular disease risks. Besides, we also collectedpatients with other cardiovascular diseases (hypertension, coronary heart disease,rheumatic heart disease and dilated cardiomyopathy) but without atrial fibrillation asa control group. Use Pearson method to do logistic regression analysis to findwhether these factors (age, left atrial diameter and left ventricular ejection fraction)may affect the onset of atrial fibrillation. 2. We extracted their DNA samples, and screening SCN5A gene by direct DNAsequencing method, include the exons and exon-intron junction regions. Then theDNA samples of200healthy individuals of the same race were also sequenced as acontrol group to identify gene mutation or gene single nucleotide polymorphism.Result：Totally125Patients with atrial fibrillation is eligible. Among them,12cases arelone atrial fibrillation,9.6%of the total numbers, other patients are combined withhypertension (68%), rheumatic heart disease (9.6%), coronary heart disease (15.2%)and dilated cardiomyopathy (4%). Logistic regression analysis showed that age(t/x2=3.046, p<0.05) and LAD (t=6.360, p<0.001) may have influence on atrialfibrillation development, the differences were statistically significant (p<0.05), andboth are risk factors of atrial fibrillation.Among aforementioned atrial fibrillation patients, a novel SCN5A geneheterozygosis missense mutation A364S was identified. This mutation is thenucleotide changed from G to T in the locus1092of SCN5A gene, lead to the364thamino acid of Nav1.5protein change from alanine to serine. We also identified8SCN5A single nucleotide polymorphisms,2novel SNPs are N1387N and M1486I,and the other6SNPs were once reported, they are A29A, H558R, P1089L, R1192Q,F1206F and D1818D, respectively.Conclusion：We firstly report that SCN5A mutation is related to atrial fibrillation in Chinesepopulation, A364S-SCN5A is a novel mutation.