Association Of Single Nucleotide Polymorphisms In SCN5A And MinK Gene With Atrial Fibrillation

Atrial Fibrillation (AF) remains a major health problem in many regions around the world. The AF is the most common arrhythmia with multi-factorial pathogenesis. A number of studies of genetic epidemiology have assessed the association of KCNQ1,KCNH2 SNPs in potassium ion channel with AF in different populations. However, few studies assessed the association sodium ion channel SNPs with AF. Mutations in the human cardiac sodium channel gene have been previously discovered in a spectrum of cardiac rhythm disorders, such as, long QT intenal syndrome,Brugadasynd,idiopathic ventrieular fibrilltion duction system disease, and sick sinus syndrome.A number of studies of genetic epidemiology have assessed the association of potassium ion channels gene with AF in different populations. However, the results are inconsistent and inconclusive. We performed a meta-analysis of the association between G112A polymorphisms of Mink gene and AF.Objective1. To investigate associations of 4 SNPs, rs6793943,rs 1805125,rs41312391,rs6599230 in SCN5A gene with AF in Chinese Han population.2. To systematic review the association between G112A polymorphisms of Mink gene, to estimate the magnitude of the gene effects.Method1. A 1:1 case-control study was carried out. SNP Genotypes was detected by SNPstream Genotyping System. A logistic regression model was used to analyze the association of SNPs with AF in all subjects and in subgroups.2. Systematic review and meta-analysis were performed to analyze the association between G112A polymorphisms in Mink gene and AF.ResultThe genotypes of rs6599230 were found to be significantly associated with AF risk (p=0.025). AA genotype (homozygous minor allele) carriers had higher risk for AF compared with GG (OR=4; 95%CI,1.37-11.64;p=0.011). We did not find significant associations of other three SNPs.In subgroup analysis, male population had higher risk for AF compared with GG (OR=12.7; 95%CI, 1.50-107.94 ;p=0.019). In female population, no significant SNP was found.2. In the meta analysis, six case-control studies with a combined 841 cases and 1079 controls were summarized for minK gene G112A. Subgroups in different races were separately analyzed. Heterogeneity and publication bias were also explored. When all groups were pooled, the individuals with G allele had a 41% higher risk of AF compared with individuals with the A allele. The GG genotype (veruse CC genotype) was found to be significant association with increased AF risk. The significant associations of AF with genotypes were also found in both dominant and recessive genetic model. In subgroup analysis, the results were consistent with above, except that the pooled OR from Chinese population was not significant in recessive genetic model.Conclusion1. Our case-control study indicated that rs6599230 may be significantly associated AF in Chinese Han population.2. Our meta-analysis suggests there may be an important effect of G112A polymorphisms in Mink gene on the pathogenesis of AF.