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Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain.
Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain.
- Source :
-
Scientific reports [Sci Rep] 2020 Feb 18; Vol. 10 (1), pp. 2806. Date of Electronic Publication: 2020 Feb 18. - Publication Year :
- 2020
-
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.
- Subjects :
- Aged
Aged, 80 and over
Female
Genome-Wide Association Study
Humans
Male
Pharmacogenetics
Polymorphism, Single Nucleotide
Prospective Studies
Spain
Acenocoumarol administration & dosage
Anticoagulants administration & dosage
Cytochrome P-450 CYP2C9 genetics
Stroke drug therapy
Vitamin K Epoxide Reductases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 32071341
- Full Text :
- https://doi.org/10.1038/s41598-020-59641-9