• Teresa Infante, Mark E Pepin, Antonio Ruocco, Ugo Trama, Ciro Mauro, and Claudio Napoli.
• Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Naples, Italy.
• Eur. J. Clin. Invest. 2024 Mar 1; 54 (3): e14135e14135.

BackgroundAlthough mounting evidence supports that aberrant DNA methylation occurs in the hearts of patients with atrial fibrillation (AF), noninvasive epigenetic characterization of AF has not yet been defined.MethodsWe investigated DNA methylome changes in peripheral blood CD4+ T cells isolated from 10 patients with AF relative to 11 healthy subjects (HS) who were enrolled in the DIANA clinical trial (NCT04371809) via reduced-representation bisulfite sequencing (RRBS).ResultsAn atrial-specific PPI network revealed 18 hub differentially methylated genes (DMGs), wherein ROC curve analysis revealed reasonable diagnostic performance of DNA methylation levels found within CDK5R1 (AUC = 0.76; p = 0.049), HSPG2 (AUC = 0.77; p = 0.038), WDFY3 (AUC = 0.78; p = 0.029), USP49 (AUC = 0.76; p = 0.049), GSE1 (AUC = 0.76; p = 0.049), AIFM1 (AUC = 0.76; p = 0.041), CDK5RAP2 (AUC = 0.81; p = 0.017), COL4A1 (AUC = 0.86; p < 0.001), SEPT8 (AUC = 0.90; p < 0.001), PFDN1 (AUC = 0.90; p < 0.01) and ACOT7 (AUC = 0.78; p = 0.032). Transcriptional profiling of the hub DMGs provided a significant overexpression of PSDM6 (p = 0.004), TFRC (p = 0.01), CDK5R1 (p < 0.001), HSPG2 (p = 0.01), WDFY3 (p < 0.001), USP49 (p = 0.004) and GSE1 (p = 0.021) in AF patients vs HS.ConclusionsCDK5R1, GSE1, HSPG2 and WDFY3 resulted the best discriminatory genes both at methylation and gene expression level. Our results provide several candidate diagnostic biomarkers with the potential to advance precision medicine in AF.© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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