Abstract 1781: Enriched Association of Chromosome 4q25 Locus With Lone Atrial Fibrillation Patients Showing Dissociated Firing After Pulmonary Vein Isolation
Atrial fibrillation (AF) has been associated with a locus on chromosome 4q25 in proximity to PITX2, a gene known to regulate left/right cardiac asymmetrical morphogenesis and implicated in the formation of pulmonary vein muscle sleeve myocardium. PITX2 may also suppress a default pathway for sinoatrial node formation in the left atrium. During AF ablation, after pulmonary vein isolation (PVI) is complete, dissociated firing (DF) reminiscent of sinoatrial node activity may be observed within the pulmonary veins. We tested the hypothesis that the top previously reported genome-wide AF-associated SNP in the 4q25 locus, rs2200733, is strongly associated with the DF phenotype.
Methods: The presence of DF after PVI was identified in patients with lone AF who underwent catheter-based PVI and were enrolled in a lone AF biorepository. DNA was genotyped for rs2200733, the top previously reported AF-associated single nucleotide polymorphism (SNP) using an Illumina SNP platform. Case-control associations were performed in case subjects with and without identified DF and in publicly accessible iControlDB population controls from Illumina. rs2200733 was also tested for association with DF within the lone AF cohort.
Results: Among 393 lone AF patients who underwent PVI, 51 had DF reported. Genotypes compared to 2971 population controls in an additive genetic model are shown in the Table⇓ and demonstrated odds ratios (OR) for association with rs2200733 of 4.23 for the DF group and 2.34 for the no DF group. Within the lone AF group, association with this SNP was significantly higher in the DF vs no DF group.
Conclusions: The lone AF DF phenotype demonstrates the highest reported odds ratio thus far for association with the previously reported top AF-associated SNP. This association is stronger than that seen in lone AF subjects without DF. These data suggest that tissues involved in independent firing within the pulmonary veins may contribute to the generation of AF.