Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain
Por:
Cullell, N, Carrera, C, Muino, E, Torres-Aguila, NP, Carcel-Marquez, J, Gonzalez-Sanchez, J, Gallego-Fabrega, C, Molina, J, Besora, S, Sotoca, J, Buongiorno, MT, Jimenez-Conde, J, Giralt-Steinhauer, E, de Torres-Chacon, R, Montaner, J, Mancha, F, Cabezas, JA, Marti-Fabregas, J, Prats-Sanchez, L, Camps-Renom, P, Purroy, F, Cambray, S, Freijo, MD, Vives-Bauz, C, Tur, S, Font, MA, Lopez-Cancio, E, Hernandez-Perez, M, Obach, V, Calleja, A, Arenillas, J, Rodriguez-Yanez, M, Castillo, J, Sobrino, T, Fernandez-Cadenas, I, Krupinski, J
Publicada:
18 feb 2020
Resumen:
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.
Filiaciones:
Cullell, N:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Univ Barcelona, Fac Med, Barcelona, Spain
Carrera, C:
Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Vall dHebron Inst Res VHIR, Neurovasc Res Lab, Barcelona, Spain
Muino, E:
Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Torres-Aguila, NP:
Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Carcel-Marquez, J:
Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Gonzalez-Sanchez, J:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Manchester Metropolitan Univ, Ctr Biosci, Sch HealthCare Sci, Manchester, Lancs, England
Gallego-Fabrega, C:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Molina, J:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Besora, S:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Sotoca, J:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Buongiorno, MT:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Jimenez-Conde, J:
Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain
Giralt-Steinhauer, E:
Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain
de Torres-Chacon, R:
Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain
Montaner, J:
Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain
Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville, CSIC,IBiS, Seville, Spain
Mancha, F:
Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain
Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville, CSIC,IBiS, Seville, Spain
Cabezas, JA:
Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain
Univ Seville, Hosp Univ Virgen del Rocio, Inst Biomed Seville, CSIC,IBiS, Seville, Spain
Marti-Fabregas, J:
Hosp Santa Creu & Sant Pau, Neurol, Barcelona, Spain
Prats-Sanchez, L:
Hosp Santa Creu & Sant Pau, Neurol, Barcelona, Spain
Camps-Renom, P:
Hosp Santa Creu & Sant Pau, Neurol, Barcelona, Spain
Purroy, F:
Univ Lleida, Hosp Univ Arnau de Vilanova Lleida, Dept Neurol, Stroke Unit, Lleida, Spain
Cambray, S:
Univ Lleida, Inst Recerca Biomed Lleida IRBLleida, Clin Neurosci Grp, Lleida, Spain
Freijo, MD:
Basurto Hosp, Neurol, Bilbao, Spain
Vives-Bauz, C:
Son Espases Univ Hosp, Res Unit, Neurobiol Lab, Illes Balears, Spain
Tur, S:
Son Espases Univ Hosp, Neurol, Illes Balears, Spain
Font, MA:
Moises Broggi Hosp, Neurol, Barcelona, Spain
Lopez-Cancio, E:
Germans Trias & Pujol Hosp, Stroke Unit, Barcelona, Spain
Hosp Univ Cent Asturias, Stroke Unit, Asturias, Spain
Hernandez-Perez, M:
Germans Trias & Pujol Hosp, Stroke Unit, Barcelona, Spain
Obach, V:
Hosp Clin Barcelona, Neurol, Barcelona, Spain
Calleja, A:
Univ Clin Hosp Valladolid, Dept Neurol, Valladolid, Spain
Arenillas, J:
Univ Clin Hosp Valladolid, Dept Neurol, Valladolid, Spain
Rodriguez-Yanez, M:
Clin Univ Hosp, Hlth Res Inst Santiago de Compostela IDIS, Dept Neurol, Clin Neurosci Res Lab, Santiago, Spain
Castillo, J:
Clin Univ Hosp, Hlth Res Inst Santiago de Compostela IDIS, Dept Neurol, Clin Neurosci Res Lab, Santiago, Spain
Sobrino, T:
Clin Univ Hosp, Hlth Res Inst Santiago de Compostela IDIS, Dept Neurol, Clin Neurosci Res Lab, Santiago, Spain
Fernandez-Cadenas, I:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Krupinski, J:
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Manchester Metropolitan Univ, Ctr Biosci, Sch HealthCare Sci, Manchester, Lancs, England
Gold, Green Published
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