TNNI3 and MYBPC3 variants in hypertrophic cardiomyopathy were associated with earlier onset, increased septal thickness, and significant alterations in amino acid and lipid metabolism.
Observational (n=108)
Are TNNI3 and MYBPC3 variants associated with specific clinical phenotypes and metabolic disorders in patients with hypertrophic cardiomyopathy?
TNNI3 and MYBPC3 variants in HCM are associated with distinct metabolic alterations, particularly in amino acid and lipid metabolism, which correlate with cardiac structure and function.
Hypertrophic cardiomyopathy is an inherited cardiovascular disease with heterogeneous presentation. However, the metabolic changes resulting from mutations and their relationship to the phenotype remain unclear. To investigate the association between TNNI3 and MYBPC3 variants and both clinical phenotype and metabolic disorders in HCM patients. 34 newly diagnosed HCM patients, 51 healthy individuals, and 23 unaffected family members were included. Clinical information and plasma samples were collected and analyzed. Whole-exome and Sanger sequencing were used for variant identification. Non-targeted metabolomics was performed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry. TNNI3 and MYBPC3 variants were identified in familial HCM cases, which exhibited earlier onset and increased interventricular septum thickness. Metabolomics revealed lower L-valine and higher free fatty acid levels in HCM patients. Patients with TNNI3 variants showed dysregulation of lyso-phosphatidylcholines and lyso-phosphatidylethanolamines, along with disturbances in glutamic acid-related pathways. MYBPC3 variants were linked to dysregulation in energy metabolism. Correlation analysis highlighted associations between specific lipid metabolites and cardiac structure and function. Significant metabolic alterations, particularly in amino acid and lipid metabolism, are prevalent in HCM. These findings enhance our understanding of HCM pathogenesis and suggest potential biomarkers and therapeutic targets for this genetic heart disease.
Wu et al. (Sat,) conducted a observational in Hypertrophic cardiomyopathy (n=108). TNNI3 and MYBPC3 variants vs. Healthy individuals and unaffected family members was evaluated on Clinical phenotype and metabolic alterations. TNNI3 and MYBPC3 variants in hypertrophic cardiomyopathy were associated with earlier onset, increased septal thickness, and significant alterations in amino acid and lipid metabolism.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: