A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia.
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.
Dhandapany
Perundurai S
PS
Department of Biochemistry, Madurai Kamaraj University, Madurai 625 021, India.
Sadayappan
Sakthivel
S
Xue
Yali
Y
Powell
Gareth T
GT
Rani
Deepa Selvi
DS
Nallari
Prathiba
P
Rai
Taranjit Singh
TS
Khullar
Madhu
M
Soares
Pedro
P
Bahl
Ajay
A
Tharkan
Jagan Mohan
JM
Vaideeswar
Pradeep
P
Rathinavel
Andiappan
A
Narasimhan
Calambur
C
Ayapati
Dharma Rakshak
DR
Ayub
Qasim
Q
Mehdi
S Qasim
SQ
Oppenheimer
Stephen
S
Richards
Martin B
MB
Price
Alkes L
AL
Patterson
Nick
N
Reich
David
D
Singh
Lalji
L
Tyler-Smith
Chris
C
Thangaraj
Kumarasamy
K
D001208:Asia; D001344:Autopsy; D001483:Base Sequence; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005843:Geography; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000502:physiology; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C