Background Atrial ﬁbrillation (AF) is the most common supraventricular tachycardia encountered in clinical practise associated with pronounced morbidity, mortality, and socio-economic burden. To date, mechanism of AF is still not fully understood but believed to be multifactorial including genetic predisposition. A number of genetic loci and genes related to the disorder have been reported. Recently, several genome-wide association studies (GWAS) have yielded associations between common sequence variants and ECG variables. SNP rs3825214, which is located in the last intron of the TBX5 gene, was shown correlating with the PR interval, the QRS duration, the QT interval and verified significant in diseases as atrial fibrillation, advanced AV block. The postulate that variants on TBX5 influence the occurrence of AF by a new mechanism different from the most extensively accepted ion channel theory may be potential possibility.
Objective The aim of this study is to futher assess association between SNP rs3825214 and ECG parametres, AF, ventricular tachycardia (VT), as well as some arrhythmias associating with sudden cardiac death (SCD) in mainland chinese han population.
Methods 692 patients as AF group, 235 patients as VT group, and 856 controls in GeneID population were enrolled for case-control association study. Peripheral blood of subjects was extracted through vein. Then cracking red blood cells, separating white blood cells, extracting genomic DNA by SDS alkali cracking method was performed. Genotyping using High Resolution Melt system was performed. The associations of both allele and genotype were analysised by accurate statistical analysis adjusting for potential confounding factors using SPSS 17.0 and PLINK v1.05.
Results Subjects form Chinese GeneID population including 692 patients as atrial fibrillation (AF) group, 235 patients as ventricular tachycardia (VT) group, and 856 controls were enrolled in the study. No signiﬁcant differences were found between the two 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, we observed the association between SNP rs3825214 and QTc (P = 0.047).
There was no deviation from the Hardy-Weinberg equilibrium for SNP rs3825214 in control groups (P = 0.8361). Neither male group nor female group was associated with allelic G of SNP rs3825214. A significant association between G allele of SNP rs3825214 and 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 AF group (60.3%), was shown no significant (P = 0.546). There was also no significant in VT group considering the total VT and other cardiovascular diseases such as bundle branch block, bradycardia, ER, hypertrophic cardiomyopathy, malignant ventricular arrhythmia. However, the assocition of G allele and AF in VT group showed a significant difference (P = 0.004). In both AF and LAF group, the distributions were significantly different compared to the control group with P value equals to 0.029 and 0.003 respectively. No significant interaction was observed between genotypes and ECG measures. Assuming a dominant genetic model, the GG shows strong significant association with AF, and especially LAF. The GG genotype could be a profond protective factor under dominant genetic model as the OR was 0.73 after adjusting for sex, age, T2DM, hypertension, stroke, and CAD.
Conclusions The study detected the association of allele G of SNP rs3825214 in TBX5 with QTc and lone AF for the first time. The ﬁndings expand the GWAS results to other ethnic population and provide new insight into the molecular aetiology involved in the pathogenesis of lone AF.