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

• Published in: Nature genetics Vol. 41; no. 2; pp. 187 - 191
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2009; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Asia; Autopsy; Base Sequence; Binding sites; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cardiology; Cardiology. Vascular system; Cardiomyopathies - genetics; Cardiomyopathies - pathology; Cardiomyopathy; Carrier Proteins - genetics; Carrier Proteins - physiology; Case-Control Studies; Cohort Studies; Developing countries; DNA Mutational Analysis; Fundamental and applied biological sciences. Psychology; Gene Frequency; Gene Function; Gene mutations; Genetic aspects; Genetic Linkage; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Geography; Health aspects; Heart; Heart diseases; Human Genetics; Humans; Industrial research; LDCs; letter; Medical sciences; Molecular Sequence Data; Myocarditis. Cardiomyopathies; Myosin; Polymorphism, Genetic - physiology; Risk factors; Studies; Asia; South Asia; Heart; Variant; Binding protein; Cardiomyopathy; Heart disease; Myosin; Cardiovascular disease; Protein C; Circulatory system; Molecular motor; Myocardial disease
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.309

Kumarasamy Thangaraj and colleagues describe the association of a 25-bp deletion in MYBPC3 with heritable cardiomyopathies in Indian populations. They find a high prevalence (4–8%) of the deletion in surveyed Indian populations and an absence of the deletion in surveyed populations outside of Southeast Asia. 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 × 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.