Effect of epigenetic regulation on left atrial function and recurrence after catheter ablation in patients with atrial fibrillation

Abstract

Abstract Background Genetic variation and modifiable risk factors play a significant role in the pathogenesis of atrial fibrillation (AF). However, the influence of epigenetic modification on AF remains to be elucidated. Methods Epigenetic evaluation was performed in 115 AF patients who underwent radiofrequency catheter ablation (RFCA) in a single institution. We measured methylation at approximately 850,000 bp cytosine-phosphate-guanine (CpG) sites in the 115 samples. Results The degree of methylation was compared across seven classification criteria: type of AF, late recurrence, impaired left atrium (LA) function, late gadolinium enhancement, LA diameter, LA volume, and flow velocity of the LA appendage. The four most significantly methylated genes in our cohort were DEFB104B, C3, TANC1, and TMEM9B. The DEFB104B gene (cg20223677 in the transcription start site), which encodes β-defensin 104B, was hypomethylated in three groups: those with late recurrence, impaired LA function, and impaired LAA flow velocity. Enriched functional annotation of the differentially methylated datasets revealed that five out of the seven AF groups in this cohort were associated with genes involved in the cell movement of endothelial cell lines, sprouting angiogenesis by endothelial cell lines, or migration of endothelial cell lines. Conclusion In this study, epigenetic profiling revealed that epigenetic modification might affect crucial traits of AF, such as the degree of atrial myopathy and treatment effects after RFCA, suggesting the hypothesis that the pathogenesis of AF might be affected by not only genetic variation or modifiable factors but also by epigenetic modulation. The identified methylation-susceptible loci can be used in targeting for epigenetic-based therapeutic agents.