CYP2C9 and VKORC1 in therapeutic dosing and safety of acenocoumarol treatment: implication for clinical practice in Hungary.
Environ Toxicol Pharmacol
; 56: 282-289, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-29055218
ABSTRACT
The purpose of this work was to investigate the contribution of CYP2C9 and VKORC1 to acenocoumarol (AC) dose variability, bleeding events in Hungary. The study recruited 117 patients on long-term AC therapy (INR 2-3), and 510 healthy individuals to model the findings. Patients were genotyped for alleles proved to affect lower AC overdose CYP2C9*2, CYP2C9*3, VKORC1*2. Additionally, we tested VKORC1*3, VKORC1*4 to examine their effect in patients with higher AC requirements. Most impact on dose reduction is accountable for CYP2C9*2/*3 (59%) and for VKORC1*2/*2 (45.5%), and on dose increase for newly evaluated VKORC1*3/*4 (22.5%) diplotypes. VKORC1*3 and *4 alleles seem to balance the dose-reducing effect of VKORC1*2 allele. Being a carrier of combination of VKORC1*2 and CYP2C9*2,*3 polymorphisms, rather than of one of these SNPs, is associated with higher risk of over-anticoagulation (up to 34.3%) in long-term AC treatment. The pharmacogenetic dosing algorithm involving VKORC1, CYP2C9 diplotypes and age explains 30.4% of AC dosing variability (p<6.10×10-9). Correlation between the studied diplotypes and bleeding events could not be revealed.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo de Nucleótido Simple
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Vitamina K Epóxido Reductasas
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Citocromo P-450 CYP2C9
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Acenocumarol
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Anticoagulantes
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País como asunto:
Europa
Idioma:
En
Año:
2017
Tipo del documento:
Article