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

AbstractLamin 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 withLMNA pathogenic mutations. The study population (N = 75) included (i) patients with pathogenicLMNA mutations responsible for fDCM (LMNAMUT), (ii) age- and sex-matchedLMNA 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 inLMNAMUT carriers and age-matchedLMNAWT controls (N = 16). Forty-four miRNAs were specifically deregulated inLMNAMUT 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 inLMNAMUT carriers compared toLMNAWT 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 betweenLMNAWT healthy subjects andLMNAMUT carriers who are phenotypically negative for DCM and betweenLMNAWT iDCM andLMNA-related DCM patien...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research