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

References

1. Reddy, K.S., Shah, B., Varghese, C. & Ramadoss, A. Responding to the threat of chronic diseases in India. Lancet 366, 1744–1749 (2005).
   Article Google Scholar
2. Joshi, P. et al. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. J. Am. Med. Assoc. 297, 286–294 (2007).
   Article CAS Google Scholar
3. Liew, C.C. & Dzau., V. J. Molecular genetics and genomics of heart failure. Nat. Rev. Genet. 5, 811–825 (2004).
   Article CAS Google Scholar
4. Flavigny, J. et al. Biomolecular interactions between human recombinant h-MyHC and cMyBP-Cs implicated in familial hypertrophic cardiomyopathy. Cardiovasc. Res. 60, 388–396 (2003).
   Article CAS Google Scholar
5. Flavigny, J. et al. 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. 294, 443–456 (1999).
   Article CAS Google Scholar
6. Gruen, M. & Gautel, M. 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. 286, 933–949 (1999).
   Article CAS Google Scholar
7. Freiburg, A. & Gautel, M. A molecular map of the interactions between titin and myosin-binding protein C. Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy. Eur. J. Biochem. 235, 317–326 (1996).
   Article CAS Google Scholar
8. Squire, J.M., Luther, P.K. & Knupp, C. Structural evidence for the interaction of C-protein (MyBP-C) with actin and sequence identification of a possible actin-binding domain. J. Mol. Biol. 331, 713–724 (2003).
   Article CAS Google Scholar
9. McClellan, G., Kulikovskaya, I. & Winegrad, S. Changes in cardiac contractility related to calcium-mediated changes in phosphorylation of myosin-binding protein C. Biophys. J. 81, 1083–1092 (2001).
   Article CAS Google Scholar
10. Sadayappan, S. et al. Cardiac myosin binding protein c phosphorylation is cardioprotective. Proc. Natl. Acad. Sci. USA 103, 16918–16923 (2006).
    Article CAS Google Scholar
11. Niimura, H. et al. Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly. Circulation 105, 446–451 (2002).
    Article CAS Google Scholar
12. Van Driest, S.L. et al. Sarcomeric genotyping in hypertrophic cardiomyopathy. Mayo Clin. Proc. 80, 463 (2005).
    Article CAS Google Scholar
13. Waldmuller, S. et al. Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy. J. Mol. Cell. Cardiol. 35, 623–636 (2003).
    Article CAS Google Scholar
14. Thanseem, I. et al. Genetic affinities among the lower castes and tribal groups of India: inference from Y chromosome and mitochondrial DNA. BMC Genet. 7, 42 (2006).
    Article Google Scholar
15. The International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007).
16. Berul, C.I. et al. Ventricular arrhythmia vulnerability in cardiomyopathic mice with homozygous mutant myosin-binding protein C gene. Circulation 104, 2734–2739 (2001).
    Article CAS Google Scholar
17. Niimura, H. et al. Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N. Engl. J. Med. 338, 1248–1257 (1998).
    Article CAS Google Scholar
18. Kubo, T. et al. 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. 46, 1737–1743 (2005).
    Article CAS Google Scholar
19. Rottbauer, W. et al. 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. 100, 475–482 (1997).
    Article CAS Google Scholar
20. Moolman, J.A. et al. 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 101, 1396–1402 (2000).
    Article CAS Google Scholar
21. Vignier, N. et al. Cardiac myosin-binding protein C and familial hypertrophic cardiomyopathy: from mutations identification to human endomyocardial proteins analysis. Circulation 104 (Suppl.), II–1 (2001).
    Google Scholar
22. Yang, Q., Osinska, H., Klevitsky, R. & Robbins, J. Phenotypic deficits in mice expressing a MyBP-C lacking the titin and myosin binding domains. J. Mol. Cell. Cardiol. 33, 1649–1658 (2001).
    Article CAS Google Scholar
23. Sarikas, A. et al. Impairment of the ubiquitin-proteasome system by truncated cardiac myosin binding protein C mutants. Cardiovasc. Res. 66, 33–44 (2005).
    Article CAS Google Scholar
24. Okada, K. et al. 4-Hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress. Identification of proteasomes as target molecules. J. Biol. Chem. 274, 23787–23793 (1999).
    Article CAS Google Scholar
25. Bulteau, A.L., Szweda, L.I. & Friguet, B. Age-dependent declines in proteasome activity in the heart. Arch. Biochem. Biophys. 397, 298–304 (2002).
    Article CAS Google Scholar
26. Sato, N. et al. 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 14, 3180–3191 (2003).
    Article CAS Google Scholar
27. Thangaraj, K. et al. Reconstructing the origin of Andaman Islanders. Science 308, 996 (2005).
    Article CAS Google Scholar
28. Gupta, R., Misra, A., Pais, P., Rastogi, P. & Gupta, V.P. Correlation of regional cardiovascular disease mortality in India with lifestyle and nutritional factors. Int. J. Cardiol. 108, 291–300 (2006).
    Article Google Scholar

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Acknowledgements

We thank all participants for making this study possible. We acknowledge the help of G.S. Selvam, C. Rajamanickam, R. Srinivasan, V. Madhavan, S. Madhavan, A.G. Reddy, A. Vanniarajan, P. Govindaraj, B.D. Gelb and Q. Long. P.S.D. was supported by Council of Scientific and Industrial Research – Senior Research Fellowship (CSIR-SRF) and P.N. by Department of Biotechnology (DBT). K.T. was supported by Council of Scientific and Industrial Research (CSIR) - Raman Research Fellowship and Y.X., G.T.P., Q.A., S.Q.M. and C.T.-S. were supported by The Wellcome Trust. T.S.R. received an Senior Research Fellowship (SRF) from Indian Council of Medical Research (ICMR), M.K. and A.B. were supported by Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh. S.S. received a post-doctoral training grant from the American Heart Association, Ohio Valley Affiliate, USA. D.R. is supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences.

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Author notes

1. Qasim Ayub & S Qasim Mehdi
   Present address: Present addresses: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK (Q.A.) and Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan (S.Q.M.).,

Authors and Affiliations

1. Department of Biochemistry, Madurai Kamaraj University, Madurai, 625 021, India
   Perundurai S Dhandapany
2. Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, 45229, Ohio, USA
   Sakthivel Sadayappan
3. Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, Cambridgeshire, UK
   Yali Xue, Gareth T Powell & Chris Tyler-Smith
4. Centre for Cellular and Molecular Biology, Hyderabad, 500 007, India
   Deepa Selvi Rani, Lalji Singh & Kumarasamy Thangaraj
5. Department of Genetics, Osmania University, Hyderabad, 500 007, India
   Prathiba Nallari
6. Post Graduate Institute of Medical Education and Research, Chandigarh, 160 012, India
   Taranjit Singh Rai, Madhu Khullar & Ajay Bahl
7. Faculty of Biological Sciences, Institute of Integrative and Comparative Biology, University of Leeds, Leeds, LS2 9JT, UK
   Pedro Soares & Martin B Richards
8. Department of Cardiology, Sri Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, 695 011, India
   Jagan Mohan Tharkan
9. Department of Pathology (Cardiovascular & Thoracic Division), Seth GS Medical College and KEM Hospital, Mumbai, 400 012, India
   Pradeep Vaideeswar
10. Department of Cardio-Thoracic Surgery, Rajaji Government Hospital and Madurai Medical College, Madurai, 625020, India
    Andiappan Rathinavel
11. Cardiology Unit, CARE Hospital, Hyderabad, 500 001, India
    Calambur Narasimhan
12. Department of Cardiac Surgery, Nizams Institute of Medical Sciences, Hyderabad, 500 082, India
    Dharma Rakshak Ayapati
13. Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Karachi, 75270, Pakistan
    Qasim Ayub & S Qasim Mehdi
14. Department of Anthropology, University of Oxford, Oxford, OX1 2JD, UK
    Stephen Oppenheimer
15. Harvard School of Public Health, Boston, 02115, Massachusetts, USA
    Alkes L Price
16. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA
    Nick Patterson & David Reich
17. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA
    David Reich

Authors

1. Perundurai S Dhandapany
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2. Sakthivel Sadayappan
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3. Yali Xue
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4. Gareth T Powell
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5. Deepa Selvi Rani
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6. Prathiba Nallari
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7. Taranjit Singh Rai
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8. Madhu Khullar
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9. Pedro Soares
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10. Ajay Bahl
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11. Jagan Mohan Tharkan
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12. Pradeep Vaideeswar
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13. Andiappan Rathinavel
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14. Calambur Narasimhan
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15. Dharma Rakshak Ayapati
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16. Qasim Ayub
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17. S Qasim Mehdi
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18. Stephen Oppenheimer
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19. Martin B Richards
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20. Alkes L Price
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21. Nick Patterson
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22. David Reich
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23. Lalji Singh
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24. Chris Tyler-Smith
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25. Kumarasamy Thangaraj
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Contributions

P.S.D., C.T.-S. and K.T. designed the study. A.B., J.M.T., P.V., A.R., C.N. and D.R.A. helped in recruitment of cardiomyopathy cases and controls. P.S.D., P.N., T.S.R., M.K. and D.S.R. screened the subject samples. P.S.D., S.S., Y.X., G.T.P., D.S.R. and K.T. performed the major experiments including genotyping, functional studies and sequencing. K.T., L.S., C.T.-S. and D.R. provided reagents for the study. K.T., C.T.-S., L.S., Q.A., S.Q.M., P.S., S.O., A.L.P., N.P. and M.B.R. helped in collecting and genotyping the various population samples. P.S.D. and K.T. drafted the manuscript with the help of C.T.-S. and D.R.

Corresponding author

Correspondence toKumarasamy Thangaraj.

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Dhandapany, P., Sadayappan, S., Xue, Y. et al. A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia.Nat Genet 41, 187–191 (2009). https://doi.org/10.1038/ng.309

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• Received: 07 July 2008
• Accepted: 03 November 2008
• Published: 18 January 2009
• Issue Date: February 2009
• DOI: https://doi.org/10.1038/ng.309