Atrial fibrillation(AF)is the most common form of clinical cardiac arrhythmia.Investigation of the pathogenic genes of AF is helpful for early screening of AF.The aim of this experiment is to screen for susceptible genes with potential pathogenic significance in both familial and non-familial AF popula-tions,and to explore their roles in the pathogenesis of AF.Firstly,whole-exome sequencing(WES)was performed to identify the gene mutation responsible for AF on 4 patients with familial AF.Then,Sanger sequencing was used to verify the susceptibility gene mutations in the patients with non-familial AF and the healthy populations.Western blotting was used to analyze their protein expression levels.Outward po-tassium-ion currents were recorded using whole-cell patch clamp technique.There are 39 individuals in the family,of which 4 have suffered from AF.These four AF patients have two identical mutated genes:FAM160A2(homozygous mutation,rs77726581 c.1375C＞T)and MUC5B(heterozygous mutation,rs199736618 c.12272C＞T).Among 52 non-familial AF patients,5 had similar heterozygous point mu-tation at the same locus of FAM160A2,but heterozygous mutations of MUC5B were found in both non-fa-milial AF and healthy populations.There was no significant difference in the protein expression level of FAM160A2 between the non-familial AF and the healthy population.The FAM160A2 gene mutation sig-nificantly reduced outward potassium ion current(compared to the wild-type,P＜0.001).Thus,FAM160A2 loss-of-function mutation may be a new molecular biological mechanism for AF,which can be used for early screening for AF.
万方数据
维普
