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

5 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

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Phospholipid Ethers
metabolome
Branched Chain Amino Acids
Metabolome
Hypertrophic Cardiomyopathy
cardiomyopathy
Metabolites
Triglycerides
Cardiac Myosins
mutation
Echocardiography
Mutation
hypertrophy
Genes
Lipids
Plasmas
branched chain amino acids
Left Ventricular Hypertrophy
Hypertrophy
ethers

Keywords

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

Cite this

Jørgenrud, B., Jalanko, M., Heliö, T., Jääskeläinen, P., Laine, M., Hilvo, M., ... Kuusisto, J. (2015). The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy. PLoS ONE, 10(8), [e0134184]. https://doi.org/10.1371/journal.pone.0134184
Jørgenrud, Benedicte ; Jalanko, Mikko ; Heliö, Tiina ; Jääskeläinen, Pertti ; Laine, Mika ; Hilvo, Mika ; Nieminen, Markku S. ; Laakso, Markku ; Hyötyläinen, Tuulia ; Oresic, Matej ; Kuusisto, Johanna. / The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy. In: PLoS ONE. 2015 ; Vol. 10, No. 8.
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title = "The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy",
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.",
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author = "Benedicte J{\o}rgenrud and Mikko Jalanko and Tiina Heli{\"o} and Pertti J{\"a}{\"a}skel{\"a}inen and Mika Laine and Mika Hilvo and Nieminen, {Markku S.} and Markku Laakso and Tuulia Hy{\"o}tyl{\"a}inen and Matej Oresic and Johanna Kuusisto",
note = "CO:U Hormone Laboratory, Aker Hospital, Oslo University Hospital, Oslo, Norway CO:U Division of Women and Children's Health, Department of Pediatric Research, Oslo University Hospital, Oslo, Norway CO:K Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland CO:K Kuopio University Hospital, Heart Center, Kuopio, Finland CO:K University of Eastern Finland, Kuopio University Hospital, Department of Medicine, Kuopio, Finland CO:U Steno Diabetes Center, Gentofte, Denmark CA2: BA3112 CA2: BA116 AU2: Hilvo, Mika AU2: Hy{\"o}tyl{\"a}inen, Tuulia AU2: Oresic, Matej ISI: MULTIDISCIPLINARY SCIENCES",
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Jørgenrud, B, Jalanko, M, Heliö, T, Jääskeläinen, P, Laine, M, Hilvo, M, Nieminen, MS, Laakso, M, Hyötyläinen, T, Oresic, M & Kuusisto, J 2015, 'The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy', PLoS ONE, vol. 10, no. 8, e0134184. https://doi.org/10.1371/journal.pone.0134184

The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy. / Jørgenrud, Benedicte; Jalanko, Mikko; Heliö, Tiina; Jääskeläinen, Pertti; Laine, Mika; Hilvo, Mika; Nieminen, Markku S.; Laakso, Markku; Hyötyläinen, Tuulia; Oresic, Matej (Corresponding Author); Kuusisto, Johanna.

In: PLoS ONE, Vol. 10, No. 8, e0134184, 2015.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy

AU - Jørgenrud, Benedicte

AU - Jalanko, Mikko

AU - Heliö, Tiina

AU - Jääskeläinen, Pertti

AU - Laine, Mika

AU - Hilvo, Mika

AU - Nieminen, Markku S.

AU - Laakso, Markku

AU - Hyötyläinen, Tuulia

AU - Oresic, Matej

AU - Kuusisto, Johanna

N1 - CO:U Hormone Laboratory, Aker Hospital, Oslo University Hospital, Oslo, Norway CO:U Division of Women and Children's Health, Department of Pediatric Research, Oslo University Hospital, Oslo, Norway CO:K Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland CO:K Kuopio University Hospital, Heart Center, Kuopio, Finland CO:K University of Eastern Finland, Kuopio University Hospital, Department of Medicine, Kuopio, Finland CO:U Steno Diabetes Center, Gentofte, Denmark CA2: BA3112 CA2: BA116 AU2: Hilvo, Mika AU2: Hyötyläinen, Tuulia AU2: Oresic, Matej ISI: MULTIDISCIPLINARY SCIENCES

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - lipid metabolism

KW - metabolites

KW - metabolomics

KW - phospholipids

KW - lipid analysis

KW - echocardiography

KW - amino acid metabolism

U2 - 10.1371/journal.pone.0134184

DO - 10.1371/journal.pone.0134184

M3 - Article

VL - 10

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 8

M1 - e0134184

ER -

Jørgenrud B, Jalanko M, Heliö T, Jääskeläinen P, Laine M, Hilvo M et al. The metabolome in finnish carriers of the MYBPC3-Q1061X mutation for hypertrophic cardiomyopathy. PLoS ONE. 2015;10(8). e0134184. https://doi.org/10.1371/journal.pone.0134184