Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain

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2020
Author
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 Garcia, Francisco
Cambray Carner, Serafí
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
Suggested citation
Cullell, Natalia; Carrera, Caty; Muiño, Elena; Torres-Aguila, Nuria-Paz; Cárcel-Márquez, Jara; González-Sánchez, Jonathan; ... Krupinski, Jerzy. (2020) . Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain. Scientific Reports, 2020, vol. 10, núm. 2806. https://doi.org/10.1038/s41598-020-59641-9.
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Abstract
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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http://hdl.handle.net/10459.1/68273
DOI
https://doi.org/10.1038/s41598-020-59641-9
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Scientific Reports, 2020, vol. 10, núm. 2806
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cc-by, (c) Cullell et al., 2020
Except where otherwise noted, this item's license is described as cc-by, (c) Cullell et al., 2020