MYBPH acts as modifier of cardiac hypertrophy in hypertrophic cardiomyopathy (HCM) patients

Hum Genet. 2016 May;135(5):477-483. doi: 10.1007/s00439-016-1649-7. Epub 2016 Mar 11.


Left ventricular hypertrophy is a risk factor for cardiovascular morbidity and mortality. Hypertrophic cardiomyopathy (HCM) is considered a model disease to study causal molecular factors underlying isolated cardiac hypertrophy. However, HCM manifests with various clinical symptoms, even in families bearing the same genetic defects, suggesting that additional factors contribute to hypertrophy. The gene encoding the cardiac myosin binding protein C (cMYBPC) is one of the most frequently implicated genes in HCM. Recently another myosin binding protein, myosin binding protein H (MYBPH) was shown to function in concert with cMYBPC in regulating cardiomyocyte contraction. Given the similarity in sequence, structure and the critical role MYBPH plays in sarcomere contraction, we proposed that MYBPH may be involved in HCM pathogenesis. Family-based genetic association analysis was employed to investigate the contribution of MYBPH in modifying hypertrophy. Seven single nucleotide polymorphisms and haplotypes in MYBPH were investigated for hypertrophy modifying effects in 388 individuals (27 families), in which three unique South African HCM-causing founder mutations (p.R403W and pA797T in β-myosin heavy chain gene (MYH7) and p.R92W in the cardiac troponin T gene (TNNT2)) segregate. We observed a significant association between rs2250509 and hypertrophy traits in the p.A797T MYH7 mutation group. Additionally, haplotype GGTACTT significantly affected hypertrophy within the same mutation group. MYBPH was for the first time assessed as a candidate hypertrophy modifying gene. We identified a novel association between MYBPH and hypertrophy traits in HCM patients carrying the p.A797T MYH7 mutation, suggesting that variation in MYBPH can modulate the severity of hypertrophy in HCM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiomegaly / etiology*
  • Cardiomyopathy, Hypertrophic / complications
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cohort Studies
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polymorphism, Genetic / genetics*
  • Prognosis


  • Cytoskeletal Proteins
  • MYBPH protein, human