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

被引：213

作者：

Dhandapany, Perundurai S. ^{[2
]}

Sadayappan, Sakthivel ^{[3
]}

Xue, Yali ^{[4
]}

Powell, Gareth T. ^{[4
]}

Rani, Deepa Selvi ^{[1
]}

Nallari, Prathiba ^{[5
]}

Rai, Taranjit Singh ^{[6
]}

Khullar, Madhu ^{[6
]}

Soares, Pedro ^{[7
]}

Bahl, Ajay ^{[6
]}

Tharkan, Jagan Mohan ^{[8
]}

Vaideeswar, Pradeep ^{[9
,11
]}

Rathinavel, Andiappan ^{[10
,12
]}

Narasimhan, Calambur ^{[13
]}

Ayapati, Dharma Rakshak ^{[14
]}

Ayub, Qasim ^{[15
]}

Mehdi, S. Qasim ^{[15
]}

Oppenheimer, Stephen ^{[16
]}

Richards, Martin B. ^{[7
]}

Price, Alkes L. ^{[17
]}

Patterson, Nick ^{[18
,19
]}

Reich, David ^{[18
,19
,20
]}

Singh, Lalji ^{[1
]}

Tyler-Smith, Chris ^{[4
]}

Thangaraj, Kumarasamy ^{[1
]}

机构：

[1] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India

[2] Madurai Kamaraj Univ, Dept Biochem, Madurai 625021, Tamil Nadu, India

[3] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA

[4] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England

[5] Osmania Univ, Dept Genet, Hyderabad 500007, Andhra Pradesh, India

[6] Postgrad Inst Med Educ & Res, Chandigarh 160012, India

[7] Univ Leeds, Fac Biol Sci, Inst Integrat & Comparat Biol, Leeds LS2 9JT, W Yorkshire, England

[8] Sri Chitra Tirunal Inst Med Sci & Technol, Dept Cardiol, Thiruvananthapuram 695011, Kerala, India

[9] Seth GS Med Coll, Dept Pathol, Cardiovasc & Thorac Div, Bombay 400012, Maharashtra, India

[10] Rajaji Govt Hosp, Dept Cardiothorac Surg, Madurai 625020, Tamil Nadu, India

[11] King Edward Mem Hosp, Bombay 400012, Maharashtra, India

[12] Madurai Med Coll, Madurai 625020, Tamil Nadu, India

[13] CARE Hosp, Cardiol Unit, Hyderabad 500001, Andhra Pradesh, India

[14] Nizams Inst Med Sci, Dept Cardiac Surg, Hyderabad 500082, Andhra Pradesh, India

[15] Univ Karachi, Inst Biotechnol & Genet Engn KIBGE, Karachi 75270, Pakistan

[16] Univ Oxford, Dept Anthropol, Oxford OX1 2JD, England

[17] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[18] Broad Inst Harvard, Cambridge, MA 02142 USA

[19] MIT, Cambridge, MA 02142 USA

[20] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 02期

关键词：

FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; SPLICE DONOR SITE; GENE; MUTATIONS; IDENTIFICATION; INDIA; PHOSPHORYLATION; IMPAIRMENT; MUTANTS; DOMAIN;

D O I：

10.1038/ng.309

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown(1). 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 = 2 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 (similar to 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.

引用

页码：187 / 191

页数：5

共 28 条

[1] Ventricular arrhythmia vulnerability in cardiomyopathic mice with homozygous mutant myosin-binding protein C gene [J].

Berul, CI ;

McConnell, RK ;

Wakimoto, H ;

Moskowitz, IPG ;

Maguire, CT ;

Semsarian, C ;

Vargas, MM ;

Gehrmann, J ;

Seidman, CE ;

Seidman, JG .

CIRCULATION, 2001, 104 (22) :2734-2739

[2] Age-dependent declines in proteasome activity in the heart [J].

Bulteau, AL ;

Szweda, LI ;

Friguet, B .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2002, 397 (02) :298-304

[3] Biomolecular interactions between human recombinant β-MyHC and cMyBP-Cs implicated in familial hypertrophic cardiomyopathy [J].

Flavigny, J ;

Robert, P ;

Camelin, JC ;

Schwartz, K ;

Carrier, L ;

Berrebi-Bertrand, I .

CARDIOVASCULAR RESEARCH, 2003, 60 (02) :388-396

[4] COOH-terminal truncated cardiac myosin-binding protein C mutants resulting from familial hypertrophic cardiomyopathy mutations exhibit altered expression and/or incorporation in fetal rat cardiomyocytes [J].

Flavigny, J ;

Souchet, M ;

Sébillon, P ;

Berrebi-Bertrand, I ;

Hainque, B ;

Mallet, A ;

Bril, A ;

Schwartz, K ;

Carrier, L .

JOURNAL OF MOLECULAR BIOLOGY, 1999, 294 (02) :443-456

[5] A second generation human haplotype map of over 3.1 million SNPs [J].

Frazer, Kelly A. ;

Ballinger, Dennis G. ;

Cox, David R. ;

Hinds, David A. ;

Stuve, Laura L. ;

Gibbs, Richard A. ;

Belmont, John W. ;

Boudreau, Andrew ;

Hardenbol, Paul ;

Leal, Suzanne M. ;

Pasternak, Shiran ;

Wheeler, David A. ;

Willis, Thomas D. ;

Yu, Fuli ;

Yang, Huanming ;

Zeng, Changqing ;

Gao, Yang ;

Hu, Haoran ;

Hu, Weitao ;

Li, Chaohua ;

Lin, Wei ;

Liu, Siqi ;

Pan, Hao ;

Tang, Xiaoli ;

Wang, Jian ;

Wang, Wei ;

Yu, Jun ;

Zhang, Bo ;

Zhang, Qingrun ;

Zhao, Hongbin ;

Zhao, Hui ;

Zhou, Jun ;

Gabriel, Stacey B. ;

Barry, Rachel ;

Blumenstiel, Brendan ;

Camargo, Amy ;

Defelice, Matthew ;

Faggart, Maura ;

Goyette, Mary ;

Gupta, Supriya ;

Moore, Jamie ;

Nguyen, Huy ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Roy, Jessica ;

Stahl, Erich ;

Winchester, Ellen ;

Ziaugra, Liuda ;

Altshuler, David ;

Shen, Yan .

NATURE, 2007, 449 (7164) :851-U3

[6] A molecular map of the interactions between titin and myosin-binding protein C - Implications for sarcomeric assembly in familial hypertrophic cardiomyopathy [J].

Freiburg, A ;

Gautel, M .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1996, 235 (1-2) :317-323

[7] Mutations in β-myosin S2 that cause familial hypertrophic cardiomyopathy (FHC) abolish the interaction with the regulatory domain of myosin-binding protein-C [J].

Gruen, M ;

Gautel, M .

JOURNAL OF MOLECULAR BIOLOGY, 1999, 286 (03) :933-949

[8] Correlation of regional cardiovascular disease mortality in India with lifestyle and nutritional factors [J].

Gupta, R ;

Misra, A ;

Pais, P ;

Rastogi, P ;

Gupta, VP .

INTERNATIONAL JOURNAL OF CARDIOLOGY, 2006, 108 (03) :291-300

[9] Risk factors for early myocardial infarction in South Asians compared with individuals in other countries [J].

Joshi, Prashant ;

Islam, Shofiqul ;

Pais, Prem ;

Reddy, Srinath ;

Dorairaj, Prabhakaran ;

Kazmi, Khawar ;

Pandey, Mrigendra Raj ;

Haque, Sirajul ;

Mendis, Shanthi ;

Rangarajan, Sumathy ;

Yusuf, Salim .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 297 (03) :286-294

[10] Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac myosin-binding protein c gene among Japanese [J].

Kubo, T ;

Kitaoka, H ;

Okawa, M ;

Matsumura, Y ;

Hitomi, N ;

Yamasaki, N ;

Furuno, T ;

Takata, J ;

Nishinaga, M ;

Kimura, A ;

Doi, YL .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2005, 46 (09) :1737-1743

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