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Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy
VTT Technical Research Centre of Finland, Espoo, Finland.
VTT Technical Research Centre of Finland, Tampere, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
Helsinki University Central Hospital, Helsinki, Finland.
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2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 1, article id e15744Article in journal (Refereed) Published
Abstract [en]

Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.

Place, publisher, year, edition, pages
Public Library of Science , 2011. Vol. 6, no 1, article id e15744
National Category
Cardiac and Cardiovascular Systems Medical Genetics
Identifiers
URN: urn:nbn:se:oru:diva-63641DOI: 10.1371/journal.pone.0015744ISI: 000286522200012PubMedID: 21283746Scopus ID: 2-s2.0-79251636741OAI: oai:DiVA.org:oru-63641DiVA, id: diva2:1169207
Note

Finnish Foundation for Cardiovascular Research  

Finnish Medical Foundation  special governmental subsidy for health sciences research TYH 7106 TYH2009121 

European Commission 201668 

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-22Bibliographically approved

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Oresic, Matej

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