Epigenetic Study of Cohort of Monozygotic Twins With Hypertrophic Cardiomyopathy Due to MYBPC3 (Cardiac Myosin-Binding Protein C).

Autor: Peñarroya A; Nanomaterials and Nanotechnology Research Center (CINN) Spanish National Research Council (CSIC) El Entrego Asturias Spain.; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain., Lorca R; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain.; Unidad de Cardiopatías Familiares, Área del Corazón y Departamento de Genética Molecular Hospital Universitario Central Asturias Oviedo Spain.; Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORs) Madrid Spain.; Departamento de Biología Funcional Universidad de Oviedo Oviedo Spain., Rodríguez Reguero JJ; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain.; Unidad de Cardiopatías Familiares, Área del Corazón y Departamento de Genética Molecular Hospital Universitario Central Asturias Oviedo Spain., Gómez J; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain.; Unidad de Cardiopatías Familiares, Área del Corazón y Departamento de Genética Molecular Hospital Universitario Central Asturias Oviedo Spain.; Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORs) Madrid Spain., Avanzas P; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain.; Unidad de Cardiopatías Familiares, Área del Corazón y Departamento de Genética Molecular Hospital Universitario Central Asturias Oviedo Spain.; Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORs) Madrid Spain.; Departamento de Medicina Universidad de Oviedo Oviedo Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV) Oviedo Spain., Tejedor JR; Nanomaterials and Nanotechnology Research Center (CINN) Spanish National Research Council (CSIC) El Entrego Asturias Spain.; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain.; Spanish Biomedical Research Network in Rare Diseases (CIBERER) Madrid Spain.; Institute of Oncology of Asturias (IUOPA), University of Oviedo Oviedo Asturias Spain., Fernandez AF; Nanomaterials and Nanotechnology Research Center (CINN) Spanish National Research Council (CSIC) El Entrego Asturias Spain.; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain.; Spanish Biomedical Research Network in Rare Diseases (CIBERER) Madrid Spain.; Institute of Oncology of Asturias (IUOPA), University of Oviedo Oviedo Asturias Spain., Fraga MF; Nanomaterials and Nanotechnology Research Center (CINN) Spanish National Research Council (CSIC) El Entrego Asturias Spain.; Health Research Institute of the Principality of Asturias (ISPA) Oviedo Asturias Spain.; Spanish Biomedical Research Network in Rare Diseases (CIBERER) Madrid Spain.; Institute of Oncology of Asturias (IUOPA), University of Oviedo Oviedo Asturias Spain.
Jazyk: angličtina
Zdroj: Journal of the American Heart Association [J Am Heart Assoc] 2024 Nov 05; Vol. 13 (21), pp. e035777. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1161/JAHA.124.035777
Abstrakt: Background: Hypertrophic cardiomyopathy is an autosomal dominant cardiac disease. The mechanisms that determine its variable expressivity are poorly understood. Epigenetics could play a crucial role in bridging the gap between genotype and phenotype by orchestrating the interplay between the environment and the genome regulation. In this study we aimed to establish a possible correlation between the peripheral blood DNA methylation patterns and left ventricular hypertrophy severity in patients with hypertrophic cardiomyopathy, evaluating the potential impact of lifestyle variables and providing a biological context to the observed changes.
Methods and Results: Methylation data were obtained from peripheral blood samples (Infinium MethylationEPIC BeadChip arrays). We employed multiple pair-matched models to extract genomic positions whose methylation correlates with the degree of left ventricular hypertrophy in 3 monozygotic twin pairs carrying the same founder pathogenic variant ( MYBPC3 p.Gly263Ter). This model enables the isolation of the environmental influence, beyond age, on DNA methylation changes by removing the genetic background. Our results revealed a more anxious personality among more severely affected individuals. We identified 56 differentially methylated positions that exhibited moderate, proportional changes in methylation associated with left ventricular hypertrophy. These differentially methylated positions were enriched in regions regulated by repressor histone marks and tended to cluster at genes involved in left ventricular hypertrophy development, such as HOXA5 , TRPC3 , UCN3 , or PLSCR2 , suggesting that changes in peripheral blood may reflect myocardial alterations.
Conclusions: We present a unique pair-matched model, based on 3 monozygotic twin pairs carrying the same founder pathogenic variant and different phenotypes. This study provides further evidence of the pivotal role of epigenetics in hypertrophic cardiomyopathy variable expressivity.
Databáze: MEDLINE
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