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 › Letter › peer-review

236 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 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.

Original language	English
Pages (from-to)	187-91
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	2
DOIs	https://doi.org/10.1038/ng.309
Publication status	Published - Feb 2009
Externally published	Yes

Keywords

Asia
Autopsy
Base Sequence
Cardiomyopathies
Carrier Proteins
Case-Control Studies
Cohort Studies
DNA Mutational Analysis
Gene Frequency
Genetic Linkage
Genetic Predisposition to Disease
Geography
Humans
Molecular Sequence Data
Polymorphism, Genetic

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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), 187-91. https://doi.org/10.1038/ng.309

@article{c1d534822d7c49f8a75685e32a44c059,

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 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.",

keywords = "Asia, Autopsy, Base Sequence, Cardiomyopathies, Carrier Proteins, Case-Control Studies, Cohort Studies, DNA Mutational Analysis, Gene Frequency, Genetic Linkage, Genetic Predisposition to Disease, Geography, Humans, Molecular Sequence Data, Polymorphism, Genetic",

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",

month = feb,

doi = "10.1038/ng.309",

language = "English",

volume = "41",

pages = "187--91",

journal = "Nature Genetics",

issn = "1061-4036",

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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. 187-91. https://doi.org/10.1038/ng.309

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

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 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.

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 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.

KW - Asia

KW - Autopsy

KW - Base Sequence

KW - Cardiomyopathies

KW - Carrier Proteins

KW - Case-Control Studies

KW - Cohort Studies

KW - DNA Mutational Analysis

KW - Gene Frequency

KW - Genetic Linkage

KW - Genetic Predisposition to Disease

KW - Geography

KW - Humans

KW - Molecular Sequence Data

KW - Polymorphism, Genetic

U2 - 10.1038/ng.309

DO - 10.1038/ng.309

M3 - Letter

C2 - 19151713

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

Abstract

Keywords

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