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PMID: 19151713 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia.

Nature genetics ·Vol. 41 ·No. 2 ·2009-02-00 ·Pages 187-91

Dhandapany PS, Sadayappan S, Xue Y, Powell GT, Rani DS, Nallari P, Rai TS, Khullar M, Soares P, Bahl A, Tharkan JM, Vaideeswar P, Rathinavel A, Narasimhan C, Ayapati DR, Ayub Q, Mehdi SQ, Oppenheimer S, Richards MB, Price AL, Patterson N, Reich D, Singh L, Tyler-Smith C, Thangaraj K

Abstract

Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown. Cardiomyopathies due to sarcomeric mutations are a major monogenic cause for heart failure (MIM600958). Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (initial study OR = 5.3 (95% CI = 2.3-13), P = 2 x 10(-6); replication study OR = 8.59 (3.19-25.05), P = 3 x 10(-8); combined OR = 6.99 (3.68-13.57), P = 4 x 10(-11)) and that disrupts cardiomyocyte structure in vitro. Its prevalence was found to be high (approximately 4%) in populations of Indian subcontinental ancestry. The finding of a common risk factor implicated in South Asian subjects with cardiomyopathy will help in identifying and counseling individuals predisposed to cardiac diseases in this region.

MeSH Terms
Asia Autopsy Base Sequence Cardiomyopathies/genetics,pathology Carrier Proteins/genetics,physiology Case-Control Studies Cohort Studies DNA Mutational Analysis Gene Frequency Genetic Linkage Genetic Predisposition to Disease Geography Humans Molecular Sequence Data Polymorphism, Genetic/physiology
Chemicals
Carrier Proteins myosin-binding protein C
Authors & Affiliations
25 authors, click to expand affiliations / ORCID
Dhandapany Perundurai S
Department of Biochemistry, Madurai Kamaraj University, Madurai 625 021, India.
Sadayappan Sakthivel
Xue Yali
Powell Gareth T
Rani Deepa Selvi
Nallari Prathiba
Rai Taranjit Singh
Khullar Madhu
Soares Pedro
Bahl Ajay
Tharkan Jagan Mohan
Vaideeswar Pradeep
Rathinavel Andiappan
Narasimhan Calambur
Ayapati Dharma Rakshak
Ayub Qasim
Mehdi S Qasim
Oppenheimer Stephen
Richards Martin B
Price Alkes L
Patterson Nick
Reich David
Singh Lalji
Tyler-Smith Chris
Thangaraj Kumarasamy
References (27)
27 references, click to expand
  1. Impairment of the ubiquitin-proteasome system by truncated cardiac myosin binding protein C mutants.
    Cardiovasc Res. 2005 Apr 1;66(1):33-44 PMID: 15769446
  2. A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance.
    Circulation. 2000 Mar 28;101(12):1396-402 PMID: 10736283
  3. Cardiac myosin binding protein C phosphorylation is cardioprotective.
    Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16918-23 PMID: 17075052
  4. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries.
    JAMA. 2007 Jan 17;297(3):286-94 PMID: 17227980
  5. Ventricular arrhythmia vulnerability in cardiomyopathic mice with homozygous mutant Myosin-binding protein C gene.
    Circulation. 2001 Nov 27;104(22):2734-9 PMID: 11723028
  6. Phenotypic deficits in mice expressing a myosin binding protein C lacking the titin and myosin binding domains.
    J Mol Cell Cardiol. 2001 Sep;33(9):1649-58 PMID: 11549344
  7. Mutations in beta-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C.
    J Mol Biol. 1999 Feb 26;286(3):933-49 PMID: 10024460
  8. A second generation human haplotype map of over 3.1 million SNPs.
    Nature. 2007 Oct 18;449(7164):851-61 PMID: 17943122
  9. Reconstructing the origin of Andaman Islanders.
    Science. 2005 May 13;308(5724):996 PMID: 15890876
  10. Genetic affinities among the lower castes and tribal groups of India: inference from Y chromosome and mitochondrial DNA.
    BMC Genet. 2006 Aug 07;7:42 PMID: 16893451
  11. Correlation of regional cardiovascular disease mortality in India with lifestyle and nutritional factors.
    Int J Cardiol. 2006 Apr 14;108(3):291-300 PMID: 15978684
  12. Biomolecular interactions between human recombinant beta-MyHC and cMyBP-Cs implicated in familial hypertrophic cardiomyopathy.
    Cardiovasc Res. 2003 Nov 1;60(2):388-96 PMID: 14613868
  13. 4-Hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress. Identification of proteasomes as target molecules.
    J Biol Chem. 1999 Aug 20;274(34):23787-93 PMID: 10446139
  14. COOH-terminal truncated cardiac myosin-binding protein C mutants resulting from familial hypertrophic cardiomyopathy mutations exhibit altered expression and/or incorporation in fetal rat cardiomyocytes.
    J Mol Biol. 1999 Nov 26;294(2):443-56 PMID: 10610770
  15. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly.
    Circulation. 2002 Jan 29;105(4):446-51 PMID: 11815426
  16. Responding to the threat of chronic diseases in India.
    Lancet. 2005 Nov 12;366(9498):1744-9 PMID: 16291069
  17. Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac Myosin-binding protein C gene among Japanese.
    J Am Coll Cardiol. 2005 Nov 1;46(9):1737-43 PMID: 16256878
  18. Changes in cardiac contractility related to calcium-mediated changes in phosphorylation of myosin-binding protein C.
    Biophys J. 2001 Aug;81(2):1083-92 PMID: 11463649
  19. Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy.
    J Mol Cell Cardiol. 2003 Jun;35(6):623-36 PMID: 12788380
  20. Sarcomeric genotyping in hypertrophic cardiomyopathy.
    Mayo Clin Proc. 2005 Apr;80(4):463-9 PMID: 15819282
  21. Molecular genetics and genomics of heart failure.
    Nat Rev Genet. 2004 Nov;5(11):811-25 PMID: 15520791
  22. Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization Of cardiac transcript and protein.
    J Clin Invest. 1997 Jul 15;100(2):475-82 PMID: 9218526
  23. Structural evidence for the interaction of C-protein (MyBP-C) with actin and sequence identification of a possible actin-binding domain.
    J Mol Biol. 2003 Aug 15;331(3):713-24 PMID: 12899839
  24. A molecular map of the interactions between titin and myosin-binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy.
    Eur J Biochem. 1996 Jan 15;235(1-2):317-23 PMID: 8631348
  25. Age-dependent declines in proteasome activity in the heart.
    Arch Biochem Biophys. 2002 Jan 15;397(2):298-304 PMID: 11795886
  26. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy.
    N Engl J Med. 1998 Apr 30;338(18):1248-57 PMID: 9562578
  27. A novel variant of cardiac myosin-binding protein-C that is unable to assemble into sarcomeres is expressed in the aged mouse atrium.
    Mol Biol Cell. 2003 Aug;14(8):3180-91 PMID: 12925755
Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.309
Published
2009-02-00
Epub
2009-00-18
Pages
187-91
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2697598
Subset
IM
Grants
Wellcome Trust · 077009 · United Kingdom
NHGRI NIH HHS · R01 HG006399 · United States
External Links
PubMed source DOI: 10.1038/ng.309 PMC Full Text View journal details
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