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Integrated Methylome and Transcriptome Analysis in Chronic Chagas Cardiomyopathy Uncovers Alterations in Heart
Francisco Heredia-Fernández1, Javier Martínez-López1,2, Laura C Terrón-Camero1
1Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
The Journal of Infectious Diseases
|July 30, 2026
Summary
Altered DNA methylation in blood may predict chronic Chagas cardiomyopathy (CCC) severity. This epigenetic signature, particularly in immune genes, reflects cardiac damage and offers potential biomarkers for Chagas disease progression.
Area of Science:
- Epigenetics and Genomics
- Infectious Diseases
- Cardiovascular Research
Background:
- Chagas disease, caused by Trypanosoma cruzi, is a global health concern.
- Chronic Chagas cardiomyopathy (CCC) leads to progressive cardiac dysfunction.
- Mechanisms driving differential CCC development are not fully understood.
Purpose of the Study:
- To investigate the role of host DNA methylation and gene expression in CCC pathogenesis.
- To identify epigenetic alterations associated with differential CCC progression.
Main Methods:
- Whole-blood DNA methylation analysis in 42 CCC patients and 23 indeterminate cases.
- Integrated transcriptomic analysis in a subset of 22 individuals.
- Transcription factor (TF) and functional enrichment analyses were performed.
Main Results:
- Severe CCC patients showed increased methylation variability, especially in immune regulation genes.
- Dysregulated genes involved in cardiac development, morphogenesis, and ion homeostasis were identified.
- GATA5 emerged as a key TF in cardiac pathways; RUNX TFs correlated with disease severity.
Conclusions:
- A systemic epigenetic signature in blood correlates with cardiac pathology in CCC.
- Findings suggest blood-based epigenetic markers for CCC.
- Potential for novel therapeutic targets to prevent Chagas disease progression.
