|
|
Plasma microRNAs as biomarkers for Lamin A/C-related dilated cardiomyopathy
|
|
|
|
|
نویسنده
|
Toro Rocío ,Blasco-Turrión Sara ,Morales-Ponce Francisco José ,Gonzalez Pablo ,Martínez-Camblor Pablo ,López-Granados Amador ,Brugada Ramon ,Campuzano Oscar ,Pérez-Serra Alexandra ,Longobardo Felix Rosa ,Mangas Alipio ,Llorente-Cortes Vicenta ,Gonzalo-Calvo David de
|
منبع
|
journal of molecular medicine - 2018 - دوره : 96 - شماره : 8 - صفحه:845 -856
|
چکیده
|
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 (lmnamut), (ii) age- and sex-matched lmna wild-type controls (lmnawt control), and (iii) lmna wild-type idiopathic dcm (idcm) patients (lmnawt 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 lmnamut carriers and age-matched lmnawt controls (n = 16). forty-four mirnas were specifically deregulated in lmnamut 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 lmnamut carriers compared to lmnawt 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 lmnawt healthy subjects and lmnamut carriers who are phenotypically negative for dcm and between lmnawt 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.
|
کلیدواژه
|
Dilated cardiomyopathy ,Lamin A/C (LMNA) ,Circulating microRNAs ,Biomarkers
|
آدرس
|
University of Cádiz, Medicine Department, Spain, Puerto Real University Hospital, Cardiology Department, Spain, Puerto Real University Hospital, Cardiology Department, Spain, Puerto Real University Hospital, Cardiology Department, Spain, Dartmouth College, USA. Universidad Autónoma de Chile, Chile, Reina Sofía University Hospital, Cardiology Department, Spain, University of Girona-IDIBGI, Spain. University of Girona, Medical Science Department, Spain. Institute of Health Carlos III, Spain, University of Girona-IDIBGI, Spain. University of Girona, Medical Science Department, Spain. Institute of Health Carlos III, Spain, Institute of Health Carlos III, Spain. University of Girona-IDIBGI, Spain, University of Cádiz, Medicine Department, Spain, Puerta del Mar University Hospital, Internal Medicine Department, Spain. University of Cádiz, Medicine Department, Spain, Institute of Health Carlos III, Spain. Biomedical Research Institute Sant Pau (IIB Sant Pau), Spain. Institute of Biomedical Research of Barcelona (IIBB), Spain, Institute of Health Carlos III, Spain. Biomedical Research Institute Sant Pau (IIB Sant Pau), Spain. Institute of Biomedical Research of Barcelona (IIBB), Spain
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|