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Targeted DNA Methylation Analysis by Next-generation Sequencing
Published on: February 24, 2015
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A pilot study on DNA methylation changes for non-invasive molecular diagnostics in heart failure
Giuditta Benincasa1, Francesco Cacciatore2, Mark E Pepin3,4
1Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania 'Luigi Vanvitelli', Naples, Italy.
ESC Heart Failure
|September 3, 2025
Summary
DNA methylation in CD4+ T cells can differentiate between ischaemic and non-ischaemic heart failure with reduced ejection fraction (HFrEF). Specific gene hypomethylation correlates with clinical features, aiding personalized prognosis for HFrEF patients.
Area of Science:
- Cardiovascular Epigenetics
- Heart Failure Pathophysiology
- T-cell Biology
Background:
- Current heart failure (HF) therapies often neglect underlying causes due to limited understanding of differential molecular pathways in HF with reduced ejection fraction (HFrEF).
- Myocardial DNA methylation alterations are potential biomarkers for HF, but cardiac tissue is scarce.
- CD4+ T lymphocytes are implicated in left ventricle remodeling, making them a potential source for biomarkers.
Purpose of the Study:
- To investigate if DNA methylation changes in circulating CD4+ T cells can differentiate between ischaemic (IsHF) and non-ischaemic (NIsHF) causes of HFrEF.
- To determine if DNA methylation levels in CD4+ T cells correlate with key clinical features in HFrEF patients.
Main Methods:
- Post hoc analysis of the PRESMET clinical trial dataset (NCT05475028).
- Integration of epigenomic data (reduced representation bisulfite sequencing) with left-ventricle interactome data.
- Identification and analysis of differentially methylated CpG positions (DMPs) in CD4+ T cells.
Main Results:
- Six network-oriented differentially methylated CpG positions (DMPs) distinguished IsHF from NIsHF patients with AUC > 0.8.
- These DMPs were significantly hypomethylated in IsHF and annotated to six genes: CKAP4, CPT1A, EIF2S2, SPTB, SYT6, and RAB11FIP1.
- Hypomethylation of EIF2S2, RAB11FIP1, and SPTB in CD4+ T cells significantly correlated with clinical parameters like VO2 max, MECKI score, left ventricle mass index, and ejection fraction in IsHF patients.
Conclusions:
- Circulating CD4+ T cell DNA methylation patterns of CKAP4, CPT1A, EIF2S2, SPTB, SYT6, and RAB11FIP1 can differentiate IsHF from NIsHF.
- Hypomethylation of EIF2S2, SPTB, and RAB11FIP1 shows significant correlation with key clinical features in IsHF.
- These findings highlight the potential of CD4+ T cell DNA methylation for enhancing personalized prognosis in HFrEF.
