| Objective:Atrial fibrillation (AF) is the most common supraventriculartachycardia encountered in clinical practice associated with pronounced morbidity,mortality, and socio-economic burden. To date, mechanism of AF is still not fullyunderstood but believed to be multifactorial including genetic predisposition. A numberof genetic loci and genes related to the disorder have been reported. Recently, severalgenome-wide association studies (GWAS) have yielded associations between commonsequence variants and ECG variables. SNP rs3825214,which is located in the last intronof the TBX5gene, was shown correlating with the PR interval, the QRS duration, theQT interval and verified significant in diseases as atrial fibrillation, advanced AV block.The postulate that variants on TBX5influence the occurrence of AF by a newmechanism different from the most extensively accepted ion channel theory may bepotential possibility. The aim of this study is to futher assess association between SNPrs3825214and ECG parametres, AF, ventricular tachycardia(VT), as well as somearrhythmias associating with sudden cardiac death (SCD) in mainland chinese hanpopulation.Methods：692patients as AF group,235patients as VT group, and856controls inGeneID population were enrolled for case-control association study. Peripheral blood ofsubjects was extracted through vein. Then cracking red blood cells, separating whiteblood cells, extracting genomic DNA by SDS alkali cracking method was performed.Genotyping using High Resolution Melt system was performed. The associations ofboth allele and genotype were analysised by accurate statistical analysis adjusting forpotential confounding factors using SPSS17.0and PLINK v1.05.Results：Subjects form Chinese GeneID population including692patients as atrialfibrillation (AF) group,235patients as ventricular tachycardia (VT) group, and856 controls were enrolled in the study. No significant differences were found between thetwo groups and control subjects with regard to gender, age. we did not find PR interval,QRS duration, QT interval significantly associated with rs3825214. Of note, weobserved the association between SNP rs3825214and QTc(P=0.047).There was no deviation from the Hardy-Weinberg equilibrium for SNP rs3825214in control groups (P=0.8361). Neither male group nor female group was associated withallelic G of SNP rs3825214. A significant association between G allele of SNPrs3825214and lone atrial fibrillation (LAF) was arresting (P=0.002; P-adj=0.001,OR=0.652). Analysis on other AF, which account for a large percentage in the AFgroup (60.3%), was shown no significant (P=0.546). There was also no significant inVT group considering the total VT and other cardiovascular diseases such as bundlebranch block, bradycardia, ER, hypertrophic cardiomyopathy, malignant ventriculararrhythmia. However, the assocition of G allele and AF in VT group showed asignificant difference (P=0.004).In both AF and LAF group, the distributions were significantly different comparedto the control group with P value equals to0.029and0.003respectively. No significantinteraction was observed between genotypes and ECG measures. Assuming a dominantgenetic model, the GG shows strong significant association with AF, and especiallyLAF. The GG genotype could be a profond protective factor under dominant geneticmodel as the OR was0.73after adjusting for sex, age, T2DM, hypertension, stroke, andCAD.Conclusions：The study detected the association of allele G of SNP rs3825214inTBX5with QTcand lone AF for the first time. The findings expand the GWAS resultsto other ethnic population and provide new insight into the molecular aetiologyinvolved in the pathogenesis of lone AF. |
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