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


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.
Hormone laboratory, Aker hospital, Oslo University Hospital, Oslo, Norway; Division of Women and Children's Health, Department of Pediatric Research, Oslo University Hospital, Oslo, Norway.
Benedicte
B
Jørgenrud
Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland.
Mikko
M
Jalanko
Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland.
Tiina
T
Heliö
Kuopio University Hospital, Heart Center, Kuopio, Finland.
Pertti
P
Jääskeläinen
Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland.
Mika
M
Laine
VTT Technical Research Centre of Finland, Espoo, Finland.
Mika
M
Hilvo
Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland.
Markku S
MS
Nieminen
University of Eastern Finland and Kuopio University Hospital, Department of Medicine, Kuopio, Finland.
Markku
M
Laakso
Steno Diabetes Center, 2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, Espoo, Finland.
Tuulia
T
Hyötyläinen
Steno Diabetes Center, 2820 Gentofte, Denmark; VTT Technical Research Centre of Finland, Espoo, Finland.
Matej
M
Orešič
University of Eastern Finland and Kuopio University Hospital, Department of Medicine, Kuopio, Finland.
Johanna
J
Kuusisto
D000328:Adult; D000483:Alleles; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D015897:Comorbidity; D004452:Echocardiography; D005260:Female; D005387:Finland; D006579:Heterozygote; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C