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Title

Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy

AuthorsBelmonte, Thalia; Mangas, Alipio; Calderon-Dominguez, María; Quezada-Feijoo, Maribel; Ramos-Sánchez, Mónica; Campuzano, Oscar; Gómez, Silvia ; Peña-Peña, María Luisa; Cubillos-Arango, Andres M.; Dominguez, Fernando; Llorente-Cortés, Vicenta; Gonzalo-Calvo, David de; Toro, Rocío
Issue DateApr-2020
PublisherElsevier BV
CitationTranslational Research 218: 1-15 (2020)
AbstractEtiology-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, n = 37) and BAG3 (BAG3, 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.
Publisher version (URL)http://dx.doi.org/10.1016/j.trsl.2020.01.003
URIhttp://hdl.handle.net/10261/224055
DOIhttp://dx.doi.org/10.1016/j.trsl.2020.01.003
Identifiersdoi: 10.1016/j.trsl.2020.01.003
issn: 1878-1810
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