Letter abstract
Nature Genetics
Published online: 18 January 2009 | doi:10.1038/ng.309
A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia
Perundurai S Dhandapany1, Sakthivel Sadayappan2, Yali Xue3, Gareth T Powell3, Deepa Selvi Rani4, Prathiba Nallari5, Taranjit Singh Rai6, Madhu Khullar6, Pedro Soares7, Ajay Bahl6, Jagan Mohan Tharkan8, Pradeep Vaideeswar9, Andiappan Rathinavel10, Calambur Narasimhan11, Dharma Rakshak Ayapati12, Qasim Ayub13,18, S Qasim Mehdi13,18, Stephen Oppenheimer14, Martin B Richards7, Alkes L Price15, Nick Patterson16, David Reich16,17, Lalji Singh4, Chris Tyler-Smith3 & Kumarasamy Thangaraj4
Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown1. 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 10-6; replication study OR = 8.59 (3.19–25.05), P = 3
10-8; combined OR = 6.99 (3.68–13.57), P = 4
10-11) and that disrupts cardiomyocyte structure in vitro. Its prevalence was found to be high (
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.
- Department of Biochemistry, Madurai Kamaraj University, Madurai 625 021, India.
- Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
- Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.
- Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.
- Department of Genetics, Osmania University, Hyderabad 500 007, India.
- Post Graduate Institute of Medical Education and Research, Chandigarh 160 012, India.
- Faculty of Biological Sciences, Institute of Integrative and Comparative Biology, University of Leeds, Leeds LS2 9JT, UK.
- Department of Cardiology, Sri Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram 695 011, India.
- Department of Pathology (Cardiovascular & Thoracic Division), Seth GS Medical College and KEM Hospital, Mumbai 400 012, India.
- Department of Cardio-Thoracic Surgery, Rajaji Government Hospital and Madurai Medical College, Madurai 625020, India.
- Cardiology Unit, CARE Hospital, Hyderabad 500 001, India.
- Department of Cardiac Surgery, Nizams Institute of Medical Sciences, Hyderabad 500 082, India.
- Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Karachi 75270, Pakistan.
- Department of Anthropology, University of Oxford, Oxford OX1 2JD, UK.
- Harvard School of Public Health, Boston, Massachusetts 02115, USA.
- Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
- Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
- 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.).
Correspondence to: Kumarasamy Thangaraj4 e-mail: thangs@ccmb.res.in