Association Of Rs17042171 At Chromosome 4q25 With Atrial Fibrillation In The Chinese Han Population From The Central Plains

Background:Atrial fibrillation(AF)is one of the most common cardiac arrhythmias in clinical practice,10%-40%of AF patients are hospitalized each year.AF is associated with five-fold increase of stroke,three-fold increase of heart failure and two-fold increase of mortality rate,thus bring an enormous financial burden on individuals and society.Although there are many studies on the pathophysiological mechanism of AF,the specific molecular mechanism of AF is still not completely clear.Previous studies have shown that the occurrence of AF is not only associated with a variety of cardiovascular risk factors such as advancing age,obesity,hypertension,diabetes,coronary heart disease,valvular heart disease and chronic kidney disease,etc but also related with genetic factors.Up to one third of patients carry common genetic mutations that predispose to AF,suggesting that there is a close relationship between the occurrence of AF and genetic factors,of which single nucleotide polymorphisms(SNPs)play an important role.Objectives:Multiple meta-analyses on a large-scale genome-wide association study identified 5 novel susceptible single nucleotide polymorphisms(SNPs)for atrial fibrillation(AF).The aim of this study was to determine the correlations of the above SNPs with AF in the Chinese Han population from the Central Plains.Methods:A total of 168 hospitalized patients,including 56 AF and 112 controls,were recruited in this case-control study.The clinical data were obtained from the medical records.All five SNPs,rs337711 in KCNN2,rs11264280 near KCNN3,rs17042171 near PITX2,rs6771157 and rs6795970 in SCNIOA,were genotyped using amplification refractory mutation system-polymerase chain reaction or direct sequencing.The ?2 test was used to compare categorical variables and preliminarily examine correlations of the genotype frequencies with AF.Subsequently,a logistic regression model was constructed to determine the associations of the SNPs with AF based on the above screened results.Odds ratios(ORs)and 95%confidence intervals(CIs)were calculated to assess the strength of the correlations.Moreover,we downloaded the genotype data from the HapMap Project for linkage disequilibrium analysis of rs17042171.Results:It was observed that AF patients were likely to be of older age and longer left atrial diameter and had more coronary artery disease and higher hypertension compared with the control group(p<0.05).Among the five SNPs,the frequency distribution of genotype AA for rs17042171 was significantly different between the AF and control group(p<0.05).After adjusting for several covariates,there was still a high risk ratio in patients with the AA genotype compared with the AC + CC genotype(OR:5.591,95%CI:2.176-14.365,p-B<0.008).Similarly,stratification analysis on the AA genotype demonstrated significant differences between rs17042171 and persistent AF.However,there were no significant correlations between AF and the control groups for the other four SNPs.Conclusion:Our findings determined that rs17042171,near PITX2 on chromosome 4q25,was associated with AF susceptibility in the Chinese Han population from the Central Plains and suggested that this SNP can provide a new strategy for clinical diagnosis in AF patients.