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 & 5 others Nick Patterson, David Reich, Lalji Singh, Chris Tyler-Smith, Kumarasamy Thangaraj

Research output: Contribution to journalLetter

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 languageEnglish
Pages (from-to)187-91
Number of pages5
JournalNature Genetics
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 2009
Externally publishedYes

Fingerprint

Cardiac Myosins
Cardiomyopathies
Heart Failure
Cardiac Myocytes
Population
Counseling
Heart Diseases
Mutation
Mortality
Genes
myosin-binding protein C

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

Cite this

Dhandapany, P. S., Sadayappan, S., Xue, Y., Powell, G. T., Rani, D. S., Nallari, P., ... 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
Dhandapany, Perundurai S ; Sadayappan, Sakthivel ; Xue, Yali ; Powell, Gareth T ; Rani, Deepa Selvi ; Nallari, Prathiba ; Rai, Taranjit Singh ; Khullar, Madhu ; Soares, Pedro ; Bahl, Ajay ; Tharkan, Jagan Mohan ; Vaideeswar, Pradeep ; Rathinavel, Andiappan ; Narasimhan, Calambur ; Ayapati, Dharma Rakshak ; Ayub, Qasim ; Mehdi, S Qasim ; Oppenheimer, Stephen ; Richards, Martin B ; Price, Alkes L ; Patterson, Nick ; Reich, David ; Singh, Lalji ; Tyler-Smith, Chris ; Thangaraj, Kumarasamy. / A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia. In: Nature Genetics. 2009 ; Vol. 41, No. 2. pp. 187-91.
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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

A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia. / Dhandapany, Perundurai S; Sadayappan, Sakthivel; Xue, Yali; Powell, Gareth T; Rani, Deepa Selvi; Nallari, Prathiba; Rai, Taranjit Singh; Khullar, Madhu; Soares, Pedro; Bahl, Ajay; Tharkan, Jagan Mohan; Vaideeswar, Pradeep; Rathinavel, Andiappan; Narasimhan, Calambur; Ayapati, Dharma Rakshak; Ayub, Qasim; Mehdi, S Qasim; Oppenheimer, Stephen; Richards, Martin B; Price, Alkes L; Patterson, Nick; Reich, David; Singh, Lalji; Tyler-Smith, Chris; Thangaraj, Kumarasamy.

In: Nature Genetics, Vol. 41, No. 2, 02.2009, p. 187-91.

Research output: Contribution to journalLetter

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

VL - 41

SP - 187

EP - 191

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -

Dhandapany PS, Sadayappan S, Xue Y, Powell GT, Rani DS, Nallari P et al. A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia. Nature Genetics. 2009 Feb;41(2):187-91. https://doi.org/10.1038/ng.309