Association Of Rs2200733, Rs251253and Rs3825214Polymorphism With Atrial Fibrillation

Atrial fibrillation (AF) is the most common tachyarrhythmia inclinical practice and its incidence increased with age.The prevalence of AFin adult is approximately0.77%in China. In Britain, about5%of the agedover65years-old and even10%of the aged over75years-old are sufferingfrom AF. Mechanisms of AF are complicated, involvied inelectrophysiological, mechanics and molecular biological mechanisms.Though many studies focused on mechanisms of AF, the pathogenesis ofAF is still unclear now. Therefore, study on cause of AF at molecular levelis necessary and important to clarify mechanisms and explore newtherapeutic and preventive measures.In recent years, studies on molecular genetics mechanisms of AF haveachieved great progresses and many evidences were improved to beassociated with AF, but correlation study between AF and genes involved inheart early development is rarely reported. Disorganized electrical activityof the pulmonary veins plays an important role in the pathogenesis ofparoxysmal atrial fibrillation. Recently some scholars reported development of the pulmonary veins could be affected by abnormalexpression of transcription factors Pitx2and Nkx2-5based on research inmouse model. TBX5is an important transcription factor in heartdevelopment. Many domestic and international studies confirmed thatmutation or abnormal expression of TBX5could result in Holt-Oramsyndrome (HOS) and human simple congenital heart disease (CHD). It isdemonstrated that rs3825214polymorphism of TBX5may be related toshort PR interval. However, few of correlation study between AF and singlenucleotide polymorphisms (SNPs) of Pitx2, Nkx2-5and TBX5in ChineseHan population was reported.207patients with and without AF were enrolled in this study. Anassociation study between SNPs and AF was performed to assess therelevance of rs2200733, rs251253and rs3825214polymorphisms and AFin the aspect of hereditism.Objectives: To investigate the association of rs2200733, rs251253andrs3825214polymorphism with AF.Methods：1. An association study was performed between rs2200733, rs251253and rs3825214single nucleotide polymorphisms (SNPs) and atrialfibrillation. According to inclusion criteria, we enrolled100patients withAF, and the control group consisted of107patients without AF.2. Genomic DNA was extracted from blood samples of all patients using a TIANamp blood DNA kit according to the standard protocol.3. The single nucleotide polymorphisms of rs2200733, rs251253andrs3825214were genotyped by polymerase chain reaction-restrictionfragment length polymorphism (PCR-RFLP) analysis.4. Specific restrictive endonucleases were used to detect the genotypeof rs2200733、rs251253and rs3825214in specimens.5. The PCR products were purified for sequencing.Results：1. The frequencies of the three kinds of genotypes (TT, CT, CC) in AFgroup and control group were21.0%,65.0%,14.0%;and29.0%,46.7%,24.3%,respectively. The distribution of genotypes in AF group and control grouphad significant difference (P=0.027), and the frequency of CT genotype issignificantly higher in AF group than that of control group (P=0.032).No significant difference in the distributions of C and T allele frequencieswas observed between two groups (P>0.05).2. The frequencies of the three kinds of genotypes(GG, AG, AA) in AFgroup and control group were70.0%,28.0%,2.0%; and70.1%,25.2%,4.7%, respectively. There was no significant difference in distribution ofgenotypes and G and A allele frequencies between two groups (P>0.05).3. The frequencies of the three kinds of genotypes (GG,AG,AA) in AFgroup and control group were28.0%,60.0%,12.0%and15.9%,50.5%,33.6%, respectively. The frequency of GG genotype was higher in AF group than that of control group (P=0.035),and the frequency of AAgenotype was significantly lower in AF group than that of control group(P<0.001).The frequency of G and A allele in AF group and control groupwere56.0%,44.0%and41.1%,48.9%, respectively. The frequency of Gallele was significantly higher in AF group than that of control group(P=0.001).Conclusions：1. There is no obvious correlation between the rs251253polymorphism with atrial fibrillation.2. Polymorphism of rs2200733is associated with the risk of AF, andCT genotype may be a susceptible genetic factor for patients with atrialfibrillation.3. rs3825214polymorphism of TBX5is associated with the risk ofatrial fibrillation. GG genotype and G allele may be possible geneticsusceptibility factors for patients with atrial fibrillation.