High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction

• Published in: Basic research in cardiology 2024-12
• Main Authors: Benincasa, Giuditta, Pepin, Mark E, Russo, Vincenzo, Cacciatore, Francesco, D'Alto, Michele, Argiento, Paola, Romeo, Emanuele, Chiappetti, Rosaria, Laezza, Nunzia, Wende, Adam R, Schiattarella, Gabriele G, Coscioni, Enrico, La Montagna, Antonietta, Amarelli, Cristiano, Maiello, Ciro, Golino, Paolo, Condorelli, Gianluigi, Napoli, Claudio
• Format: Article
• Language: English
• ISSN: 1435-1803; 1435-1803
• DOI: 10.1007/s00395-024-01093-7

Novel biomarkers are needed to better identify-and distinguish-heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4 T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.e., discovery/validation) each of both male and female patients with HFpEF (n = 12/10), HF with reduced EF (HFrEF; n = 7/5), and volunteers lacking clinical evidence of HF (CON; n = 7/5). RRBS is the gold-standard platform for measuring genome-wide DNA methylation changes at single-cytosine resolution in hypothesis-generating studies. We identified three hypomethylated HFpEF-specific differentially methylated positions (DMPs) associated with FOXB1, ELMOD1, and DGKH genes wherein ROC curve analysis revealed that increased expression levels had a reasonable diagnostic performance in predicting HFpEF (AUC ≥ 0.8, p