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Serum circular RNAs act as blood-based biomarkers for hypertrophic obstructive cardiomyopathy

AuthorsSonnenschein, Kristina; Wilczek, Adriana Luisa; Gonzalo-Calvo, David de; Pfanne, Angelika; Derda, Anselm A.; Zwadlo, Carolin; Bavendiek, Udo; Bauersachs, Johann; Fiedler, Jan; Thum, Thomas
Issue Date30-Dec-2019
PublisherNature Publishing Group
CitationScientific Reports 9: 20350 (2019)
AbstractHypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and is associated with a high risk of sudden cardiac death. HCM is characterized by pronounced hypertrophy of cardiomyocytes, fiber disarray and development of fibrosis and can be divided into a non-obstructive (HNCM) and obstructive form (HOCM) therefore requiring personalized therapeutic therapies. In the present study, we investigated the expression patterns of several circulating circular RNAs (circRNAs) as potential biomarkers in patients with HCM. We included 64 patients with HCM and 53 healthy controls to the study and quantitatively measured the expression of a set of circRNAs already known to be associated with cardiac diseases (circDNAJC6) and/or being highly abundant in blood (circTMEM56 and circMBOAT2). Abundancy of circRNAs was then correlated to relevant clinical parameters. Serum expression levels of circRNAs DNAJC6, TMEM56 and MBOAT2 were downregulated in patients with HCM. The inverse association between circRNA levels and HCM remained unchanged even after adjusting for confounding factors. All circRNAs, evaluated separately or in combination, showed a robust discrimination capacity when comparing control subjects with HCM, HNCM or HOCM patients (AUC from 0.722 to 0.949). Two circRNAs, circTMEM56 and circDNAJC6, significantly negatively correlated with echocardiographic parameters for HOCM. Collectively, circulating circRNAs DNAJC6, TMEM56 and MBOAT2 can distinguish between healthy and HCM patients. In addition, circTMEM56 and circDNAJC6 could serve as indicators of disease severity in patients with HOCM. Thus, circRNAs emerge as novel biomarkers for HCM facilitating the clinical decision making in a personalized manner.
Publisher version (URL)http://dx.doi.org/10.1038/s41598-019-56617-2
Identifiersdoi: 10.1038/s41598-019-56617-2
e-issn: 2045-2322
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