Genome-wide association study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain

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• dc.contributor.author Cullell, Natalia
• dc.contributor.author Jiménez Conde, Jordi
• dc.contributor.author Giralt-Steinhauer, Eva
• dc.contributor.author Krupinski, Jerzy
• dc.date.accessioned 2021-04-27T06:20:17Z
• dc.date.available 2021-04-27T06:20:17Z
• dc.date.issued 2020
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cullell N, Carrera C, Muiño E, Torres-Aguila NP, Cárcel-Márquez J, González-Sánchez J, et al. Genome-wide association study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain. Sci Rep. 2020 Feb 18; 10(1): 2806. DOI: 10.1038/s41598-020-59641-9
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-020-59641-9
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/47211
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights Copyright © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Hemorràgia cerebral
• dc.subject.other Anticoagulants (Medicina)
• dc.subject.other Genoma humà
• dc.title Genome-wide association study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion