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

Perundurai S. Dhandapany; Sakthivel Sadayappan; Yali Xue; Gareth T. Powell; Deepa Selvi Rani; Prathiba Nallari; Taranjit Singh Rai; Madhu Khullar; Pedro Soares; Ajay Bahl; Jagan Mohan Tharkan; Pradeep Vaideeswar; Andiappan Rathinavel; Calambur Narasimhan; Dharma Rakshak Ayapati; Qasim Ayub; S. Qasim Mehdi; Stephen Oppenheimer; Martin B. Richards; Alkes L. Price; Nick Patterson; David Reich; Lalji Singh; Chris Tyler-Smith; Kumarasamy Thangaraj

doi:10.1038/ng.309

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

Perundurai S. Dhandapany
, Sakthivel Sadayappan
, Yali Xue
, Gareth T. Powell
, Deepa Selvi Rani
, Prathiba Nallari
, Taranjit Singh Rai
, Madhu Khullar
, Pedro Soares
, Ajay Bahl
, Jagan Mohan Tharkan
, Pradeep Vaideeswar
, Andiappan Rathinavel
, Calambur Narasimhan
, Dharma Rakshak Ayapati
, Qasim Ayub
, S. Qasim Mehdi
, Stephen Oppenheimer
, Martin B. Richards
, Alkes L. Price

Nick Patterson, David Reich, Lalji Singh, Chris Tyler-Smith, Kumarasamy Thangaraj

Research output: Contribution to journal › Article › peer-review

248 Citations (Scopus)

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 × 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.

Original language	English
Pages (from-to)	187-191
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	2
DOIs	https://doi.org/10.1038/ng.309
Publication status	Published (in print/issue) - 1 Feb 2009

Funding

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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Dhandapany, P. S., Sadayappan, S., Xue, Y., Powell, G. T., Rani, D. S., Nallari, P., Rai, T. S., Khullar, M., Soares, P., Bahl, A., Tharkan, J. M., Vaideeswar, P., Rathinavel, A., Narasimhan, C., Ayapati, D. R., Ayub, Q., Mehdi, S. Q., Oppenheimer, S., Richards, M. B., ... Thangaraj, K. (2009). A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia. Nature Genetics, 41(2), 187-191. https://doi.org/10.1038/ng.309

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title = "A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia",

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 × 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.",

author = "Dhandapany, \{Perundurai S.\} and Sakthivel Sadayappan and Yali Xue and Powell, \{Gareth T.\} and Rani, \{Deepa Selvi\} and Prathiba Nallari and Rai, \{Taranjit Singh\} and Madhu Khullar and Pedro Soares and Ajay Bahl and Tharkan, \{Jagan Mohan\} and Pradeep Vaideeswar and Andiappan Rathinavel and Calambur Narasimhan and Ayapati, \{Dharma Rakshak\} and Qasim Ayub and Mehdi, \{S. Qasim\} and Stephen Oppenheimer and Richards, \{Martin B.\} and Price, \{Alkes L.\} and Nick Patterson and David Reich and Lalji Singh and Chris Tyler-Smith and Kumarasamy Thangaraj",

year = "2009",

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doi = "10.1038/ng.309",

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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 2009, 'A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia', Nature Genetics, vol. 41, no. 2, pp. 187-191. https://doi.org/10.1038/ng.309

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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

PY - 2009/2/1

Y1 - 2009/2/1

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 - https://www.scopus.com/pages/publications/59149087665

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 -

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

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