Abstract
RationaleMutations in MYBPC3 encoding cardiac myosin binding protein C are common genetic cause of hereditary cardiac myopathies. An intronic 25-bp deletion in MYBPC3 at 3′ region is associated with dilated (DCM) and hypertrophic (HCM) cardiomyopathies in Southeast Asia. However, the frequency of MYBPC3 25 bp deletion and associated clinical presentation has not been established in an unrelated cohort of left ventricular dysfunction (LVD) secondary to coronary artery disease (CAD) patients.ObjectiveWe sought to determine the role of MYBPC3 25 bp polymorphism on LVD in two cohorts of CAD patients.Methods and ResultsThe study included 265 consecutive patients with angiographically confirmed CAD and 220 controls. MYBPC3 25 bp polymorphism was determined by polymerase chain reaction. Our results showed that carrier status of MYBPC3 25 bp deletion was associated with significant compromised left ventricle ejection fraction (LVEF ≤45) in CAD patients (p value = <0.001; OR = 4.49). To validate our results, we performed a replication study in additional 140 cases with similar clinical characteristics and results again confirmed consistent findings (p = 0.029; OR = 3.3). Also, presence of the gene deletion did not have significant association in CAD patients with preserved ejection fraction (LVEF>45) (p value = 0.1; OR = 2.3).ConclusionThe frequency of MYBPC3 DW genotype and D allele was associated with compromised LVEF implying that genetic variants of MYBPC3 encoding mutant structural sarcomere protein could increase susceptibility to left ventricular dysfunction. Therefore, 25 bp deletion in MYBPC3 may represent a genetic marker for cardiac failure in CAD patients from Southeast Asia.
Highlights
Coronary artery disease (CAD) is defined as atherosclerotic blockage[1] of arteries, supplying oxygen rich blood to the myocardium, is the most common cause of fatality, disability and economic loss, in industrialized countries
Our results showed that carrier status of MYBPC3 25 bp deletion was associated with significant compromised left ventricle ejection fraction (LVEF #45) in CAD patients (p value =,0.001; OR = 4.49)
The frequency of MYBPC3 DW genotype and D allele was associated with compromised LV ejection fraction (LVEF) implying that genetic variants of MYBPC3 encoding mutant structural sarcomere protein could increase susceptibility to left ventricular dysfunction
Summary
Coronary artery disease (CAD) is defined as atherosclerotic blockage[1] of arteries, supplying oxygen rich blood to the myocardium (heart muscle), is the most common cause of fatality, disability and economic loss, in industrialized countries. While the signs and symptoms of coronary artery disease are noted in advanced state of disease, most individuals remain asymptomatic for decades. Major complication that some CAD patients face over time is the development of Left Ventricle dysfunction (LVD). The LVD usually leads to heart failure, arrhythmias and other cardiovascular complications. Extensive atherosclerotic disease and large myocardial infarction are traditional predictors of LVD. In clinical practice, it is observed that some CAD patients who do not have such complications but still develop LVD, whereas others with well-defined predictors do not develop LV dysfunction, which is quite puzzling
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