Validation of circulating miR-323a-3p and miR-625-3p to classify hypertrophic cardiomyopathy in Friedreich's ataxia
Por:
Ibáñez-Cabellos JS, Baviera-Muñoz R, Alemany-Perna B, Sivera R, Bataller L, César-Díaz S, González-Cabo P, García-Giménez JL, Pallardó FV and Seco-Cervera M
Publicada:
13 may 2026
Ahead of Print:
1 may 2026
Resumen:
Friedreich's ataxia (FRDA) is an inherited neurodegenerative disorder frequently complicated by hypertrophic cardiomyopathy (HCM), a major cause of morbidity and mortality in these patients. Conventional protein biomarkers, such as high-sensitivity troponin or collagen turnover markers, provide only modest diagnostic accuracy, highlighting the need for more sensitive tools. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers, but independent validation in FRDA remains limited. We analyzed a cohort of FRDA patients (n = 34) and age-, sex-, and race-matched healthy controls (n = 34). Expression of a previously proposed miRNA signature was evaluated in plasma using RT-qPCR, with normalization to miR-16-5p, replicating prior methodology. Echocardiographic parameters were compared across subgroups. Associations between differential miRNA expression, comorbidities (diabetes mellitus, cardiomyopathy), and echocardiographic measures were evaluated. Receiver Operating Characteristic (ROC) curves and multivariable logistic regression assessed diagnostic performance. Five of seven candidate miRNAs were validated as differentially expressed in FRDA compared with controls. Among patients, miR-128-3p, miR-130b-5p, miR-151a-5p, miR-330-3p, and miR-142-3p were significantly up-regulated in those with diabetes. For cardiomyopathy, both miR-323a-3p (previously described by our group) and miR-625-3p showed strong associations. A multivariable model combining miR-323a-3p and miR-625-3p achieved promising discriminative performance for HCM (Area Under the Curve (AUC) = 0.84; sensitivity 80%; specificity 71.4%), outperforming traditional protein biomarkers. This two-miRNA panel offers robust non-invasive prediction of HCM in FRDA and highlights metabolic miRNAs as dual biomarkers for diabetes comorbidity. Prospective longitudinal studies and development of standardized diagnostic kits are warranted to integrate miRNA profiling into FRDA clinical care.
Filiaciones:
Ibáñez-Cabellos JS:
Department of Physiology, Medicine and Dentistry School, University of Valencia, Av. Blasco Ibáñez, 15, 46010, Valencia, Spain
Consortium Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
INCLIVA Health Research Institute, INCLIVA, Valencia, Spain
Baviera-Muñoz R:
Department of Neurology, Hospital de Manises, Manises, Spain
Alemany-Perna B:
Unit of Ataxias, Spastic Paraparesis, and Rare Neurological Diseases, Neurology Service, Hospital Universitari de Girona Dr. Josep Trueta (Girona) and Hospital de Santa Caterina (Salt), Girona, Spain
Sivera R:
Consortium Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
Neuromuscular and Ataxia Diseases Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain
Bataller L:
Department of Neurology, Instituto Valenciano de Oncología, Valencia, Spain
César-Díaz S:
Arrhythmia, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Barcelona, Spain
González-Cabo P:
Department of Physiology, Medicine and Dentistry School, University of Valencia, Av. Blasco Ibáñez, 15, 46010, Valencia, Spain
Consortium Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
INCLIVA Health Research Institute, INCLIVA, Valencia, Spain
García-Giménez JL:
Department of Physiology, Medicine and Dentistry School, University of Valencia, Av. Blasco Ibáñez, 15, 46010, Valencia, Spain
Consortium Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
INCLIVA Health Research Institute, INCLIVA, Valencia, Spain
Pallardó FV:
Department of Physiology, Medicine and Dentistry School, University of Valencia, Av. Blasco Ibáñez, 15, 46010, Valencia, Spain
Consortium Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
INCLIVA Health Research Institute, INCLIVA, Valencia, Spain
Seco-Cervera M:
Department of Physiology, Medicine and Dentistry School, University of Valencia, Av. Blasco Ibáñez, 15, 46010, Valencia, Spain
Consortium Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Valencia, Spain
INCLIVA Health Research Institute, INCLIVA, Valencia, Spain
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