A Pilot Observation On Whether DNA Methylation Regulates The Correlation Between Rs2200733 And Atrial Fibrillation

BackgroundClassical genetics believe that certain single nucleotide polymorphisms?SNPs?are strongly associated with atrial fibrillation,such as rs2200733,the molecular mechanism is still unclear.In addition,numerous studies have reported that epigenetics may be involved in the regulation of SNPs and gene phenotype,such as DNA methylation,but their association with AF is rarely reported.By reviewing the literature,we did not find any reports of DNA methylation and atrial fibrillation in the vicinity of the rs2200733 locus.ObjectiveWe investigated the impact of the variant rs2200733 on atrial fibrillation?AF?and observed whether the methylation degree of the two CpG loci located in the downstream of rs2200733 was in correlation with the mutation locus in Chinese Han individuals from central plains of China.MethodsWe recruited 238 patients from Department of Cardiology,Zhengzhou No.7 People's Hospital between September 2016 and June 2017 and divided them into two groups,the AF group and the sinus rhythm?SR?group.For all patients,peripheral venous blood samples were collected and extracted for the DNA.The approach for the genotyping of rs2200733 was the amplification refractory mutation system.We randomly selected 57 AF and 110 SR patients in the above two groups to perform bisulfite treatment and pyro-sequencing.Relevant clinical information on all patients was obtained from medical records.ResultsWe analyzed the patient's clinical data,and observed that sex,age,coronary artery disease?CAD?,diabetes mellitus?DM?,stroke,left atrial diameter?LAD?and left ventricular ejection fraction?LVEF?had impacts on AF.The?² tests showed that rs2200733 was significantly associated with AF in five genetic models,especially the recessive genetic model?OR:2.396,95%CI:1.336 to 4.297,P=0.003?.Using the online genotype analysis software SNPStats,we also found that there was significant difference in the distribution of the SNP in AF and SR groups in recessive model,even after adjustment for sex,age,CAD,DM,stroke,LAD and LVEF?OR:4.75,95%CI:2.07 to 10.91,pSNP<0.0056?.Through methylation experiment,we detected that both the CpG1 and CpG2were highly methylated.According to the results from the binary logistic regression analysis,we found that the above two loci were not associated with rs2200733 and had no effect on AF?P>0.025?.ConclusionsIn the Han population from the central plains of China,the distribution of rs2200733is consistent with the distribution of this locus in other Asian populations,and there is a correlation between rs2200733 and AF.The DNA methylation of CpG₁ and CpG₂ loci which located downstream of rs2200733 are not associated with this SNP and may not be involved in the regulation of SNP on AF.