The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy

Benedicte Jørgenrud, Mikko Jalanko, Tiina Heliö, Pertti Jääskeläinen, Mika Laine, Mika Hilvo, Markku S. Nieminen, Markku Laakso, Tuulia Hyötyläinen, Matej Oresic (Corresponding Author), Johanna Kuusisto

Research output: Contribution to journalArticleScientificpeer-review

6 Citations (Scopus)

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.
Original languageEnglish
Article numbere0134184
JournalPLoS ONE
Volume10
Issue number8
DOIs
Publication statusPublished - 2015
MoE publication typeA1 Journal article-refereed

Keywords

  • lipid metabolism
  • metabolites
  • metabolomics
  • phospholipids
  • lipid analysis
  • echocardiography
  • amino acid metabolism

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