Correlation between MYBPC3 mutation and Circulating concentrations of a marker of type I collagen metabolism on hypertrophic cardiomyopathy

Abstract

Human carriers of hypertrophic cardiomyopathy associated sarcomeric mutations have abnormal collagen metabolism before overt left ventricular hypertrophy is detectable. This study investigated whether differences in collagen biomarkers were present in blood samples in positive for the MYBPC3 mutation compared with others sarcomeric mutations. 69 subjects were recruited for hypertrophic cardiomyopathy screening using echocardiography and genotyping. Circulating markers of collagen N-terminal propeptide of type III procollagen [type III collagen synthesis]), metalloproteinase (MMP3) and specific tissue inhibitor TIPM2 and cardiac biomarkers (N-terminal B-type natriuretic peptide) were measured. Correlation between concentrations of collagen biomarkers and echocardiographic variables was analyzed, and collagen biomarker concentrations were compared between MYBPC3 mutation positive and negative subjects with left ventricular hypertrophy and mutation on others sarcomeric genes. Linear regression analyses showed that mutation carriers genotype was independently associated with collagene peptide concentration and was higher (425.4 ± 122 μg/L,) than non-carriers (214.6 ± 98.5 μg/L; P = 0.0024). Collagene petide was correlated to the LV mass and left atrium volume ( r = 0.624, P = 0.001; and r = 0.588, P = 0.002). Circulating collagen peptide was higher in MYBPC3-positive subjects than negative controls and may indicate altered collagen metabolism. Further studies are necessary to determine whether alterations in circulating collagen biomarker concentration relate to an early stage of hypertrophic cardiomyopathy.