Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain.
Acenocoumarol
/ administration & dosage
Aged
Aged, 80 and over
Anticoagulants
/ administration & dosage
Cytochrome P-450 CYP2C9
/ genetics
Female
Genome-Wide Association Study
Humans
Male
Pharmacogenetics
Polymorphism, Single Nucleotide
Prospective Studies
Spain
Stroke
/ drug therapy
Vitamin K Epoxide Reductases
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 02 2020
18 02 2020
Historique:
received:
24
09
2019
accepted:
08
01
2020
entrez:
20
2
2020
pubmed:
20
2
2020
medline:
20
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32071341
doi: 10.1038/s41598-020-59641-9
pii: 10.1038/s41598-020-59641-9
pmc: PMC7028945
doi:
Substances chimiques
Anticoagulants
0
CYP2C9 protein, human
EC 1.14.13.-
Cytochrome P-450 CYP2C9
EC 1.14.13.-
VKORC1 protein, human
EC 1.17.4.4
Vitamin K Epoxide Reductases
EC 1.17.4.4
Acenocoumarol
I6WP63U32H
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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