Drug metabolism data as secondary findings from genome sequencing for patients with cardiomyopathies

Le résumé fourni par la source

Introduction The genomics era enables more robust and sophisticated hereditary disorders diagnostics. High throughout genetic testing generates much more data than clinical situation needs, but this additional information may support patient management by identifying alternative diagnoses, disease risks, and pharmacogenomic variants affecting drug metabolism. Aim To evaluate genome wide next generation sequencing (NGS) data usefulness for guiding cardiovascular drug therapy in patients with hypertrophic (HCM) and dilated cardiomyopathies (DCM). Methods Patients with HCM and DCM consulted in LSMU Kauno Klinikos (2019–2025) with negative cardiogenetic panel NGS results were selected for genome wide testing. Single nucleotide variants in genes (VKORC1, CYP2C19, CYP2C9, SLCO1B1) relevant to cardiovascular drug metabolism were assessed with PharmCAT tool [1]. Clinical recommendations were based on CPIC guidelines [2]. Results Genome sequencing was performed in 140 patients (91 HCM, 49 DCM; 71.4% male; mean age 54.5±9.6 years). Clinically actionable pharmacogenomic variants for cardiovascular drugs were identified in 111 (79.3%) cases. Detailed analysis showed: 37 patients with intermediate/poor CYP2C9 metabolism and 74 with increased VKORC1 sensitivity (suggesting lower warfarin dose at the treatment initiation); 26 of these had atrial fibrillation who could been treated with such medication. SLCO1B1 variants, associated with increased atorvastatin, rosuvastatin toxicity risk, were found in 54 patients. Five HCM patients had non-functional CYP2C19, indicating reduced clopidogrel activation and increased exposure to mavacamten which is used for obstructive HCM treatment. Conclusions Pharmacogenomic data derived from genome-wide NGS may significantly improve drug safety and efficacy in cardiomyopathy patients by enabling personalized therapy and reducing adverse drug reactions.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.