Influence of proton pump inhibitors and VKORC1 mutations on CYP2C9-mediated dose requirements of vitamin K antagonist therapy: a pilot study.
Br J Haematol
; 167(4): 547-53, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25142093
ABSTRACT
Interindividual variations in dose requirements of oral vitamin K antagonists (VKA) are attributed to several factors, including genetic variant alleles of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9), but also interaction with co-medications. In this context, proton pump inhibitor (PPI)-related alterations of VKA maintenance dose requirements have been published. The present investigation aimed to test for an interaction profile of oral VKA-therapy and PPIs in relation to the CYP2C9 genotype. Median weekly stable VKA dose requirements over 1 year were recorded in 69 patients. Patients were genotyped for CYP2C9*2, CYP2C9*3, VKORC1c.-1639G>A and VKORC1c.174-136C>T and assessed for an association with PPI use and total VKA maintenance dose requirements. PPI users with CYP2C9 genetic variations required significantly lower weekly VKA maintenance doses than those with the wild-type genotype (t-test P = 0·02). In contrast, in subjects without PPI use, the CYP2C9 genotype had no significant influence on oral VKA dose requirements. Further, the combined CYP2C9/VKORC1 genotype was a significant predictor for VKA dose requirements [linear regression estimate -1·47, standard error 0·58 (P = 0·01)]. In conclusion, in carriers of CYP2C9 gene variations, the interference with the VKA metabolism is modified by PPI co-medication and the VCKORC1 genotype. Preceding knowledge of the genetic profile and the awareness for potentially occurring severe over-anticoagulation problems under PPI co-medication could contribute to a safer and personalized VKA pharmacotherapy.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Vitamina K
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Inibidores da Bomba de Prótons
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Vitamina K Epóxido Redutases
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Citocromo P-450 CYP2C9
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Genótipo
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Anticoagulantes
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Áustria