Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy
Por:
Belmonte, T, Mangas, A, Calderon-Dominguez, M, Quezada-Feijoo, M, Ramos, M, Campuzano, O, Gomez, S, Pena, ML, Cubillos-Arango, AM, Dominguez, F, Llorente-Cortes, V, de Gonzalo-Calvo, D, Toro, R
Publicada:
1 abr 2020
Resumen:
Etiology-based diagnosis of dilated cardiomyopathy (DCM) is challenging. We evaluated whether peripheral microRNAs (miRNAs) could be used to characterize the DCM etiology. We investigated the miRNA plasma profiles of 254 subjects that comprised 5 groups: Healthy subjects (n = 70), idiopathic DCM patients (n = 55), ischemic DCM patients (n = 60) and 2 groups of patients with pathogenic variants responsible for familial DCM in the LMNA (LMNA(MUT), n = 37) and BAG3 (BAG3(MUT), n = 32) genes. Diagnostic performance was assessed using receiver operating characteristic curves. In a screening study (n = 30), 179 miRNAs robustly detected in plasma samples were profiled in idiopathic DCM and carriers of pathogenic variants. After filtering, 26 miRNA candidates were selected for subsequent quantification in the whole study population. In the validation study, a 6-miRNA panel identified familial DCM with an AUC (95% confidence interval (CI)) of 87.8 (82.0-93.6). The 6-miRNA panel also distinguished between specific DCM etiologies with AUCs ranging from 85.9 to 89.9. Only 1 to 10 of the subjects in the first and second tertiles of the 6-miRNA panel were patients with familial DCM. Additionally, a 5-miRNA panel showed an AUC (95% CI) of 87.5 (80.4-94.6) for the identification of carriers with pathogenic variants who were phenotypically negative for DCM. The 5-miRNA panel discriminated between carriers and healthy controls with AUCs ranging from 83.2 to 90.8. Again, only 1 to 10 of the subjects in the lowest tertiles of the 5-miRNA panel were carriers of pathogenic variants. In conclusion, miRNA signatures could be used to rule out patients with pathogenic variants responsible for DCM.
Filiaciones:
Belmonte, T:
Univ Cadiz, Puerta del Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiBICA, Res Unit, Cadiz, Spain.
Mangas, A:
Puerta del Mar Univ Hosp, Internal Med Dept, Cadiz, Spain.
Univ Cadiz, Puerta del Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiBICA, Res Unit, Cadiz, Spain.
Univ Cadiz, Sch Med, Med Dept, Cadiz, Spain.
Calderon-Dominguez, M:
Univ Cadiz, Puerta del Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiBICA, Res Unit, Cadiz, Spain.
Quezada-Feijoo, M:
Alfonso X Univ, Cardiol Dept, Madrid, Spain.
Cruz Roja Hosp, Cardiol Dept, Madrid, Spain.
Ramos, M:
Alfonso X Univ, Cardiol Dept, Madrid, Spain.
Cruz Roja Hosp, Cardiol Dept, Madrid, Spain.
Campuzano, O:
Inst Hlth Carlos III, CIBERCV, Madrid, Spain.
Univ Barcelona, Hosp Clin, Biochem & Mol Genet Dept, IDIBAPS, Barcelona, Spain.
Univ Girona, Cardiovasc Genet Ctr, IDIBGI, Girona, Spain.
Univ Girona, Sch Med, Med Sci Dept, Girona, Spain.
Gomez, S:
Virgen del Rocio Universitary Hosp, Cardiol Dept, Seville, Spain.
Pena, ML:
Virgen del Rocio Universitary Hosp, Cardiol Dept, Seville, Spain.
Cubillos-Arango, AM:
Gen Univ Hosp Consortium Valencia, Valencia, Spain.
Dominguez, F:
Inst Hlth Carlos III, CIBERCV, Madrid, Spain.
Univ Cadiz, Puerta del Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiBICA, Res Unit, Cadiz, Spain.
Llorente-Cortes, V:
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain.
CSIC, Inst Biomed Res Barcelona IIBB, Barcelona, Spain.
Inst Hlth Carlos III, CIBERCV, Madrid, Spain.
de Gonzalo-Calvo, D:
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain.
CSIC, Inst Biomed Res Barcelona IIBB, Barcelona, Spain.
Inst Hlth Carlos III, CIBERCV, Madrid, Spain.
Toro, R:
Univ Cadiz, Puerta del Mar Univ Hosp, Biomed Res & Innovat Inst Cadiz INiBICA, Res Unit, Cadiz, Spain.
Univ Cadiz, Sch Med, Med Dept, Cadiz, Spain.
Puerta de Hierro Univ Hosp, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, Madrid, Spain.
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