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Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain.
Cullell, Natalia; Carrera, Caty; Muiño, Elena; Torres-Aguila, Nuria-Paz; Cárcel-Márquez, Jara; González-Sánchez, Jonathan; Gallego-Fabrega, Cristina; Molina, Jessica; Besora, Sarah; Sotoca, Javier; Buongiorno, Maria-Teresa; Jiménez-Conde, Jordi; Giralt-Steinhauer, Eva; de Torres-Chacón, Reyes; Montaner, Joan; Mancha, Fernando; Cabezas, Juan A; Martí-Fàbregas, Joan; Prats-Sánchez, Luis; Camps-Renom, Pol; Purroy, Francisco; Cambray, Serafi; Freijo, María Del Mar; Vives-Bauzá, Cristòfol; Tur, Silvia; Font, Maria-Àngels; López-Cancio, Elena; Hernandez-Perez, Maria; Obach, Victor; Calleja, Ana; Arenillas, Juan; Rodríguez-Yáñez, Manuel; Castillo, José; Sobrino, Tomas; Fernández-Cádenas, Israel; Krupinski, Jerzy.
Afiliación
  • Cullell N; Neurology, Hospital Universitari MútuaTerrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain.
  • Carrera C; Stroke Pharmacogenomics and Genetics, Biomedical Research Institute Sant Pau, Barcelona, Spain.
  • Muiño E; Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
  • Torres-Aguila NP; Stroke Pharmacogenomics and Genetics, Biomedical Research Institute Sant Pau, Barcelona, Spain.
  • Cárcel-Márquez J; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
  • González-Sánchez J; Stroke Pharmacogenomics and Genetics, Biomedical Research Institute Sant Pau, Barcelona, Spain.
  • Gallego-Fabrega C; Stroke Pharmacogenomics and Genetics, Biomedical Research Institute Sant Pau, Barcelona, Spain.
  • Molina J; Stroke Pharmacogenomics and Genetics, Biomedical Research Institute Sant Pau, Barcelona, Spain.
  • Besora S; Neurology, Hospital Universitari MútuaTerrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain.
  • Sotoca J; Centre for bioscience, School of HealthCare Science, Manchester Metropolitan University, Manchester, UK.
  • Buongiorno MT; Neurology, Hospital Universitari MútuaTerrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain.
  • Jiménez-Conde J; Stroke Pharmacogenomics and Genetics, Biomedical Research Institute Sant Pau, Barcelona, Spain.
  • Giralt-Steinhauer E; Neurology, Hospital Universitari MútuaTerrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain.
  • de Torres-Chacón R; Neurology, Hospital Universitari MútuaTerrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain.
  • Montaner J; Neurology, Hospital Universitari MútuaTerrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain.
  • Mancha F; Neurology, Hospital Universitari MútuaTerrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain.
  • Cabezas JA; Neurology, Hospital del Mar Medical Research Institute, Barcelona, Spain.
  • Martí-Fàbregas J; Neurology, Hospital del Mar Medical Research Institute, Barcelona, Spain.
  • Prats-Sánchez L; Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.
  • Camps-Renom P; Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville & Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.
  • Purroy F; Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville & Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.
  • Cambray S; Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville & Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.
  • Freijo MDM; Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Vives-Bauzá C; Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Tur S; Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Font MÀ; Stroke Unit, Department of Neurology, Universitat de Lleida, Hospital Universitari Arnau de Vilanova de Lleida, Lleida, Spain.
  • López-Cancio E; Clinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), Universitat de Lleida, Lleida, Spain.
  • Hernandez-Perez M; Neurology, Basurto Hospital, Bilbao, Spain.
  • Obach V; Neurobiology Laboratory, Research Unit, Son Espases University Hospital, Illes Balears, Spain.
  • Calleja A; Neurology, Son Espases University Hospital, Illes Balears, Spain.
  • Arenillas J; Neurology, Moisès Broggi Hospital, Barcelona, Spain.
  • Rodríguez-Yáñez M; Stroke Unit, Germans Trias i Pujol Hospital, Barcelona, Spain.
  • Castillo J; Stroke Unit, Hospital Universitario Central de Asturias, Asturias, Spain.
  • Sobrino T; Stroke Unit, Germans Trias i Pujol Hospital, Barcelona, Spain.
  • Fernández-Cádenas I; Neurology, Hospital Clinic, Barcelona, Spain.
  • Krupinski J; Department of Neurology, University Clinical Hospital of Valladolid, Valladolid, Spain.
Sci Rep ; 10(1): 2806, 2020 02 18.
Article en En | MEDLINE | ID: mdl-32071341
Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p < 0.05). Six polymorphisms were associated with stroke recurrence and four variants with ICH (p < 0.05). In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dose, stroke recurrence and ICH in a Spanish cohort. These results highlight the relevance of studying pharmacogenetics associated with efficacy and safety of anticoagulant drugs and justify studies with larger sample size and different ethnic populations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Accidente Cerebrovascular / Vitamina K Epóxido Reductasas / Citocromo P-450 CYP2C9 / Acenocumarol / Anticoagulantes Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male País/Región como asunto: Europa Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Accidente Cerebrovascular / Vitamina K Epóxido Reductasas / Citocromo P-450 CYP2C9 / Acenocumarol / Anticoagulantes Tipo de estudio: Clinical_trials / Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male País/Región como asunto: Europa Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido