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Plasma microRNAs as biomarkers for Lamin A/C-related dilated cardiomyopathy

dc.contributor.authorToro R.
dc.contributor.authorBlasco-Turrión S.
dc.contributor.authorMorales-Ponce F.J.
dc.contributor.authorGonzalez P.
dc.contributor.authorMartínez-Camblor P.
dc.contributor.authorLópez-Granados A.
dc.contributor.authorBrugada R.
dc.contributor.authorCampuzano O.
dc.contributor.authorPérez-Serra A.
dc.contributor.authorRosa Longobardo F.
dc.contributor.authorMangas A.
dc.contributor.authorLlorente-Cortes V.
dc.contributor.authorde Gonzalo-Calvo D.
dc.date.accessioned2020-09-02T22:29:17Z
dc.date.available2020-09-02T22:29:17Z
dc.date.issued2018
dc.identifier10.1007/s00109-018-1666-1
dc.identifier.citation96, 8, 845-856
dc.identifier.issn09462716
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6401
dc.descriptionAbstract: Lamin A/C gene (LMNA)-related familial dilated cardiomyopathy (fDCM) is an aggressive heart disease that often leads to transplantation and sudden death. The aim of our study was to evaluate the circulating microRNA (miRNA) profiles of patients with LMNA pathogenic mutations. The study population (N = 75) included (i) patients with pathogenic LMNA mutations responsible for fDCM (LMNA MUT ), (ii) age- and sex-matched LMNA wild-type controls (LMNA WT control), and (iii) LMNA wild-type idiopathic DCM (iDCM) patients (LMNA WT iDCM). Detailed clinical information was obtained from each participant. A panel of 179 plasma miRNAs was evaluated using RT-qPCR. An initial screening study was performed in LMNA MUT carriers and age-matched LMNA WT controls (N = 16). Forty-four miRNAs were specifically deregulated in LMNA MUT carriers. Ten miRNA candidates were selected for subsequent validation after coexpression analyses and filtered for expression levels and statistical significance. Among the candidates, let-7a-5p, miR-142-3p, miR-145-5p and miR-454-3p levels were significantly increased in LMNA MUT carriers compared to LMNA WT controls and iDCM patients (P < 0.050). These circulating miRNAs, and their combination, were also associated with the presence of pathogenic mutations in regression and ROC analyses. This signature also discriminates between LMNA WT healthy subjects and LMNA MUT carriers who are phenotypically negative for DCM and between LMNA WT iDCM and LMNA-related DCM patients. Correlation and functional enrichment analyses supported their association with the pathophysiology of the disease. We demonstrated for the first time that a specific miRNA signature could serve as a novel non-invasive tool to assist in the diagnosis of patients with fDCM caused by LMNA pathogenic mutations. Key messages: Let-7a-5p, miR-142-3p, miR-145-5p and miR-454-3p are differentially expressed in LMNA MUT carriers.A composite score based on these miRNAs is a biomarker of mutations in the LMNA gene.This miRNA signature can be associated with the pathophysiology of familial DCM.The circulating miRNA profile can assist in the diagnosis of familial DCM. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
dc.language.isoen
dc.publisherSpringer Verlag
dc.subjectBiomarkers
dc.subjectCirculating microRNAs
dc.subjectDilated cardiomyopathy
dc.subjectLamin A/C (LMNA)
dc.subjectcirculating microRNA
dc.subjectgenomic DNA
dc.subjectlamin A
dc.subjectlamin C
dc.subjectlet 7a
dc.subjectmicroRNA
dc.subjectmicroRNA 125a
dc.subjectmicroRNA 142
dc.subjectmicroRNA 145
dc.subjectmicroRNA 154
dc.subjectmicroRNA 185
dc.subjectmicroRNA 191
dc.subjectmicroRNA 197
dc.subjectmicroRNA 27a
dc.subjectmicroRNA 28
dc.subjectmicroRNA 423
dc.subjectmicroRNA 454
dc.subjectunclassified drug
dc.subjectbiological marker
dc.subjectcirculating microRNA
dc.subjectlamin A
dc.subjectmicroRNA
dc.subjecttranscriptome
dc.subjectadult
dc.subjectArticle
dc.subjectcongestive cardiomyopathy
dc.subjectcontrolled study
dc.subjectdisease association
dc.subjectfemale
dc.subjecthuman
dc.subjectlimit of detection
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmutation
dc.subjectpathophysiology
dc.subjectreal time polymerase chain reaction
dc.subjectreverse transcription polymerase chain reaction
dc.subjectwild type
dc.subjectallele
dc.subjectamino acid substitution
dc.subjectbiology
dc.subjectblood
dc.subjectcongestive cardiomyopathy
dc.subjectechocardiography
dc.subjectgene expression profiling
dc.subjectgenetic predisposition
dc.subjectgenetics
dc.subjectgenotype
dc.subjectheart function test
dc.subjectmiddle aged
dc.subjectreceiver operating characteristic
dc.subjectAdult
dc.subjectAlleles
dc.subjectAmino Acid Substitution
dc.subjectBiomarkers
dc.subjectCardiomyopathy, Dilated
dc.subjectCirculating MicroRNA
dc.subjectComputational Biology
dc.subjectEchocardiography
dc.subjectFemale
dc.subjectGene Expression Profiling
dc.subjectGenetic Predisposition to Disease
dc.subjectGenotype
dc.subjectHeart Function Tests
dc.subjectHumans
dc.subjectLamin Type A
dc.subjectMale
dc.subjectMicroRNAs
dc.subjectMiddle Aged
dc.subjectMutation
dc.subjectROC Curve
dc.subjectTranscriptome
dc.titlePlasma microRNAs as biomarkers for Lamin A/C-related dilated cardiomyopathy
dc.typeArticle


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