RT Journal Article
T1 Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy.
A1 Belmonte, Thalia
A1 Mangas, Alipio
A1 Calderon-Dominguez, Maria
A1 Quezada-Feijoo, Maribel
A1 Ramos, Monica
A1 Campuzano, Oscar
A1 Gomez, Silvia
A1 Peña, Maria Luisa
A1 Cubillos-Arango, Andres M
A1 Dominguez, Fernando
A1 Llorente-Cortes, Vicenta
A1 Gonzalo-Calvo, David de
A1 Toro, Rocio
AB 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 (LMNAMUT, n = 37) and BAG3 (BAG3MUT, 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.
PB Elsevier
YR 2020
FD 2020-01-21
LK http://hdl.handle.net/10668/15068
UL http://hdl.handle.net/10668/15068
LA en
NO Belmonte T, Mangas A, Calderon-Dominguez M, Quezada-Feijoo M, Ramos M, Campuzano O, et al. Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy. Transl Res. 2020 Apr;218:1-15
NO DdG-C was a recipient of a Juan de la Cierva-Incorporacion grant from the Ministry of Science Innovation and Universities (IJCI-2016-29393). CIBER Cardiovas cular (to OC, VLl-C and DdG-C) is an initiative from Instituto Salud Carlos III. Genetic lab is supported by Obra Social “La Caixa Foundation” (ID 100010434),Fondo Investigacion Sanitaria (FIS, PI17/01690) from Instituto Salud Carlos III, and “Fundacio Privada Daniel Bravo Andreu”. This work was supported by grants in the framework of the Integrated Territorial Initiative (ITI PI0048-2017, PI0033-2019) and a clinical research grant of the Spanish Society of Cardiology. We thank all the clinical staff who participated in the study; specially mention to Dr Ana Garcia, Dr Sergi Cesar, and Amparo Navarro. All authors have read the journal’s authorship agreement and policy on disclosure of potential conflicts of interest. DdGC, VLl-C, RT, and AM have filed a pat ent on microRNAs as biomarkers. The other authors have nothing to declare.
DS RISalud
RD Apr 5, 2025