TY - JOUR
T1 - A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia
AU - Dhandapany, Perundurai S.
AU - Sadayappan, Sakthivel
AU - Xue, Yali
AU - Powell, Gareth T.
AU - Rani, Deepa Selvi
AU - Nallari, Prathiba
AU - Rai, Taranjit Singh
AU - Khullar, Madhu
AU - Soares, Pedro
AU - Bahl, Ajay
AU - Tharkan, Jagan Mohan
AU - Vaideeswar, Pradeep
AU - Rathinavel, Andiappan
AU - Narasimhan, Calambur
AU - Ayapati, Dharma Rakshak
AU - Ayub, Qasim
AU - Mehdi, S. Qasim
AU - Oppenheimer, Stephen
AU - Richards, Martin B.
AU - Price, Alkes L.
AU - Patterson, Nick
AU - Reich, David
AU - Singh, Lalji
AU - Tyler-Smith, Chris
AU - Thangaraj, Kumarasamy
N1 - Funding Information:
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.
PY - 2009/2
Y1 - 2009/2
N2 - 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 × 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.
AB - 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 × 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.
UR - http://www.scopus.com/inward/record.url?scp=59149087665&partnerID=8YFLogxK
U2 - 10.1038/ng.309
DO - 10.1038/ng.309
M3 - Article
C2 - 19151713
AN - SCOPUS:59149087665
SN - 1061-4036
VL - 41
SP - 187
EP - 191
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -