title: Role of common sarcomeric gene polymorphisms in genetic susceptibility to left ventricular dysfunction.
abstract: Mutations in sarcomeric genes are common genetic cause of cardiomyopathies. An intronic 25-bp deletion in cardiac myosin binding protein C (MYBPC3) at 3' region is associated with dilated and hypertrophic cardiomyopathies in Southeast Asia. However, the frequency of sarcomeric gene polymorphisms and associated clinical presentation have not been established with left ventricular dysfunction (LVD). Therefore, the aim of the present study was to explore the association of MYBPC3 25-bp deletion, titin (TTN) 18 bp I/D, troponin T type 2 (TNNT2) 5 bp I/D and myospryn K2906N polymorphisms with LVD. This study includes 988 consecutive patients with angiographically confirmed coronary artery disease (CAD) and 300 healthy controls. Among the 988 CAD patients, 253 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as LVD. MYBPC3 25-bp deletion, TTN 18 bp I/D and TNNT2 5 bp I/D polymorphisms were determined by direct polymerase chain reaction method, while myospryn K2906N polymorphism by TaqMan assay. Our results showed that MYBPC3 25-bp deletion polymorphism was significantly associated with elevated risk of LVD (LVEF <45) (healthy controls versus LVD: OR=3.85, P <0.001; and nonLVD versus LVD: OR=1.65, P = 0.035), while TTN 18 bp I/D, TNNT2 5 bp I/D and myospryn K2906N polymorphisms did not show any significant association with LVD. The results also showed that MYBPC3 25-bp deletion polymorphism was significantly associated with other parameters of LV remodelling, i.e. LV dimensions (LV end diastole dimension, LVEDD: P = 0.037 and LV end systolic dimension, LVESD: P = 0.032). Our data suggests that MYBPC3 25-bp deletion may play significant role in conferring LVD as well as CAD risk in north Indian population.
authors.affiliation: Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226 014, India. balraj@sgpgi.ac.in.
authors.forename: Surendra
authors.initials: S
authors.lastname: Kumar
authors.forename: Avshesh
authors.initials: A
authors.lastname: Mishra
authors.forename: Anshika
authors.initials: A
authors.lastname: Srivastava
authors.forename: Mansi
authors.initials: M
authors.lastname: Bhatt
authors.forename: N
authors.initials: N
authors.lastname: Garg
authors.forename: S K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: Shantanu
authors.initials: S
authors.lastname: Pande
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D064211:Connectin / Q000235:genetics; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D013318:Stroke Volume; D020107:Troponin T / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D064211:Connectin; D009124:Muscle Proteins; D020107:Troponin T; D000099163:Myosin Binding Protein C; C430866:CMYA5 protein, human; C545568:TNNT2 protein, human; C577285:TTN protein, human