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Small-RNA sequencing identifies serum microRNAs associated with abnormal electrocardiography findings in patients with Chagas disease.
J. Infect. 91:106613 (2025)
BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects around 6-7 million people in Latin America and hundreds of thousands in the United States and Europe. A main complication of chronic Chagas disease is cardiomyopathy, possibly manifesting as arrhythmias, heart failure, or sudden cardiac death. Understanding the link between T. cruzi infection and cardiomyopathy is essential for early diagnosis and adequate treatment. METHODS: We sequenced small RNAs in serum samples from 228 Chagas patients recruited in Chile, Bolivia and Italy. After bioinformatic processing of sequencing data to quantify serum miRNA expression, robust logistic regression was applied to identify miRNAs differentially expressed in Chagas patients with abnormalities in electrocardiography (ECG), bundle-branch block on ECG, and high Kuschnir scores. We also investigated the association between genotype-based miRNA expression and the risk of abnormal ECG findings. FINDINGS: As reported, the risk of abnormal ECG findings was higher in male patients and increased with age. Three miRNAs showed lower serum expression levels in patients with abnormal ECG: miRNA-101-3p, miRNA-576-3p and miRNA-629-5p (p < 0.0002), especially in patients with high Kuschnir scores. The expression of miRNA-629-5p was negatively correlated with the CCL5 expression (p = 3.7×10-8), a chemokine frequently reported in Chagas disease, gene enrichment analyses indicated involvement of cytokine signalling in Chagas cardiomyopathy. INTERPRETATION: The findings demonstrate the potential of circulating miRNAs as diagnostic biomarkers for Chagas cardiomyopathy. The associations found with disease severity and immune response may help to improve our knowledge of complications' development in Chagas disease.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Biomarkers ; C-c Motif Chemokine Ligand 5 (ccl5) ; Cardiomyopathy ; Chagas ; Microrna ; Small-rna Sequencing; Randomized-trial; Heart-failure; Cardiomyopathy; Ccl5; Benznidazole; Diagnosis; Profile; Panther; Design
ISSN (print) / ISBN
0163-4453
e-ISSN
0163-4453
Journal
Journal of Infection
Quellenangaben
Volume: 91,
Issue: 4,
Article Number: 106613
Publisher
Elsevier
Publishing Place
32 Jamestown Rd, London Nw1 7by, England
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
Grants
Italian Ministry of Health "Ricerca Corrente-L2" to IRCCS Sacro Cuore Don Calabria Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Boston University
Division of Intramural Research, NHLBI
Center for Population Studies, NHLBI
NIH/NHLBI
Baden-Wuerttemberg Ministry of Science, Research, and the Arts (MWK)
German Research Foundation (DFG)
Research Council of Norway
South-Eastern Regional Health Authority
EU-LAC Health project
National Heart, Lung, and Blood Institute (NHLBI)
Boston University
Division of Intramural Research, NHLBI
Center for Population Studies, NHLBI
NIH/NHLBI
Baden-Wuerttemberg Ministry of Science, Research, and the Arts (MWK)
German Research Foundation (DFG)
Research Council of Norway
South-Eastern Regional Health Authority
EU-LAC Health project