Genetic Analysis Of Variants In The Gene SCN4B With Atrial Fibrillation

Atrial fibrillation (AF) is characterized by fast and irregular electrical activity of theatria and it is the most common arrhythmia in the clinical setting. The incidence of AF inthe total population is0.4%-1%, and the ratio increases with age. AF is a major risk factorfor ischemic stroke and heart failure, the life quality of AF patients decreased. With aconsiderable mortality and morbidity, AF is responsible for a profound socioeconomicburden.Apart from some familial atrial fibrillation as monogenic inheritance disorder, themajority of atrial fibrillation presents a complex genetic model, which is caused by geneticfactors, environmental factors, and their interactions. There are mainly three kinds ofmethods used to genetic study of AF, including familybased linkage analysis, candidategene study and genome wide association study (GWAS). Mutiple genges have beenidentified, of which most are genes code for ion channels, including potassium, calciumand sodium channel.The cardiac sodium channel is mainly consist of a pore-forming alpha subunit andauxiliary beta subunits, selectively allows sodium ions through plasma membranes, andplays an important role in the generation and propagation of the cardiac action potential.Mutations associated with AF have been identified in ion channel subunits includingcardiac sodium channel α subunit gene SCN5A, β1subunit gene SCN1B, β2subunit geneSCN2B, β3subunit gene SCN3B. We tested the hypothesis that AF is associated withSCN4B.In480unrelated AF Patients, the entire coding sequence of SCN4B were screenedby high resolution melt analysis (HRM) combined with sequencing technology. Asynonymous mutation (C798T) was found in the fifth exon and a rare SNP rs149868494(MAF＜0.005) in the first exon was found AG heterozygote in four AF patients, whichcause the corresponding amino to mutate from Gly to Ser. We increased the AF patient to944and981controls. Using candidate gene associate study, we found the minor allele Aof SNP rs149868494in SCN4B was a significant risk of AF in Chinese Han population(P=0.014, OR=3.663). The genotypic association of SNP rs149868494and AF was more significant under additive or dominant model (P=0.001, OR=3.676)This study indicates significant association between a rare coding SNPrs149868494in SCN4B and AF in Chinese Han population. The result suggests thatSCN4B is a susceptibility gene for AF.