PPM1A Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients

Background and Purpose-Despite great efforts by pharmacogenetic studies, the causes of aspirin failure to prevent the recurrence of ischemic events remain unclear. Our aim was to study whether epigenetics could be associated with the risk of vascular recurrence in aspirin-treated stroke patients. Me...

Descripción completa

Detalles Bibliográficos
Autores: Gallego-Fabrega, C, Carrera, C, Reny, JL, Fontana, P, Slowik, A, Pera, J, Pezzini, A, Serrano-Heras, G, Segura, T, Bin Dukhyil, AAA, Marti-Fabregas, J, Muino, E, Cullell, N, Montaner, J, Krupinski, J, Fernandez-Cadenas, I
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p7176
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=7176
Access Level:acceso abierto
Palabra clave:aspirin
methylation
phenotype
platelet aggregation
stroke
Descripción
Sumario:Background and Purpose-Despite great efforts by pharmacogenetic studies, the causes of aspirin failure to prevent the recurrence of ischemic events remain unclear. Our aim was to study whether epigenetics could be associated with the risk of vascular recurrence in aspirin-treated stroke patients. Methods-We performed an epigenetic joint analysis study in 327 patients treated with aspirin. In the discovery stage, we performed a nested case-control study in 38 matched ischemic stroke patients in whom 450000 methylation sites were analyzed. Nineteen patients presented vascular recurrence after stroke, and 19 matched patients did not present vascular recurrence during the first year of follow-up. In a second stage, 289 new patients were analyzed by EpiTYPER. Results-The following 3 differentially methylated candidate CpG sites, were identified in the discovery stage and analyzed in the second stage: cg26039762 (P=9.69x10(-06), RAF1), cg04985020 (P=3.47x10(-03), PPM1A), and cg08419850 (P=3.47x10(-03), KCNQ1). Joint analysis identified an epigenome-wide association for cg04985020 (PPM1A; P=1.78x10(-07)), with vascular recurrence in patients treated with aspirin. Conclusions-The pattern of differential methylation in PPM1A is associated with vascular recurrence in aspirin-treated stroke patients.