The Metabolome in Finnish Carriers of the MYBPC3-Q1061X Mutation for Hypertrophic Cardiomyopathy

PLoS One. 2015 Aug 12;10(8):e0134184. doi: 10.1371/journal.pone.0134184. eCollection 2015.

Abstract

Aims: Mutations in the cardiac myosin-binding protein C gene (MYBPC3) are the most common genetic cause of hypertrophic cardiomyopathy (HCM) worldwide. The molecular mechanisms leading to HCM are poorly understood. We investigated the metabolic profiles of mutation carriers with the HCM-causing MYBPC3-Q1061X mutation with and without left ventricular hypertrophy (LVH) and non-affected relatives, and the association of the metabolome to the echocardiographic parameters.

Methods and results: 34 hypertrophic subjects carrying the MYBPC3-Q1061X mutation, 19 non-hypertrophic mutation carriers and 20 relatives with neither mutation nor hypertrophy were examined using comprehensive echocardiography. Plasma was analyzed for molecular lipids and polar metabolites using two metabolomics platforms. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction in subjects with the MYBPC3-Q1061X mutation.

Conclusions: Our study implicates the potential role of branched chain amino acids, triglycerides and ether phospholipids in HCM, as well as suggests an association of these metabolites with remodeling and dysfunction of the left ventricle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles*
  • Cardiomyopathy, Hypertrophic / diagnosis
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / metabolism*
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Cluster Analysis
  • Comorbidity
  • Echocardiography
  • Female
  • Finland
  • Heterozygote*
  • Humans
  • Hypertrophy, Left Ventricular / genetics
  • Lipid Metabolism
  • Male
  • Metabolome*
  • Metabolomics
  • Middle Aged
  • Mutation*
  • Phenotype

Substances

  • Carrier Proteins
  • myosin-binding protein C

Grants and funding

The work was supported by the following: The Finnish Foundation of Cardiovascular Research (31.3.2007; 19.3.2009; 23.3.2010; 22.3.2012) to J.K., URL: http://www.sydantutkimussaatio.fi/welcome-to-the-finnish-foundation-for-cardiovascular-research/?lang=en; The special governmental subsidy for health sciences research of the University Hospital of Kuopio (5101048/2009; 5101056/2012) to J.K., URL: https://www.psshp.fi/web/en/frontpage; The Finnish Academy (114396/2006) to J.K., URL: http://www.aka.fi/en-GB/A/; The Finnish Medical Foundation to T. Heliö, URL: http://www.european-funding-guide.eu/scholarship/14778-scholarship; The special governmental subsidy for health sciences research of the University Hospital of Helsinki (TYH2012120; TYH2014208) to T. Heliö, URL: http://www.hyksin.com/en/index.php/Company/Helsinki%20University%20Hospital; The Aarne Koskelo Foundation to M.J., URL: http://www.aarnekoskelonsaatio.fi/; and The Research Council of Norway (214191) to B.J., URL: http://www.forskningsradet.no/en/Home_page/1177315753906. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.