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2007•Revue Médicale SuisseOpen access

Anticoagulation orale et pharmacogénétique: perspectives pour la pratique clinique

Patrick R. Benusiglio, Jules Desmeules, Pierre Dayer

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Abstract

Single nucleotide polymorphisms (SNPs) in genes encoding cytochrome P450 enzyme 2C9 (CYP2C9) and Vitamin K epoxide reductase subunit I (VKORC1) make a significant contribution to the inter-individual variability in the maintenance dose of vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon). Doses requirements in CYP2C9*2 and CYP2C9*3 heterozygotes are reduced by 8-16% and 20-36%, respectively. SNP g-1639a in VKORC1 is also associated with vitamin K antagonists dosage since heterozygotes ga and homozygotes aa require respectively 21-28% and 27-56% less warfarin or acenocoumarol than homozygotes gg. CYP2C9 and VKORC1 account for up to half the variability in vitamin K antagonists requirements and incorporating genotying data for these two genes into dosing algorithms could lead to a safer anticoagulation therapy.

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What this paper is about

Single nucleotide polymorphisms (SNPs) in genes encoding cytochrome P450 enzyme 2C9 (CYP2C9) and Vitamin K epoxide reductase subunit I (VKORC1) make a significant contribution to the inter-individual variability in the maintenance dose of vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon). Doses requirements in CYP2C9*2 and CYP2C9*3 heterozygotes are reduced by 8-16% and 20-36%, respectively. SNP g-1639a in VKORC1 is also associated with vitamin K antagonists dosage since heterozygotes ga and homozygotes aa require respectively 21-28% and 27-56% less warfarin or acenocoumarol than homozygotes gg. CYP2C9 and VKORC1 account for up to half the variability in vitamin K antagonists requirements and incorporating genotying data for these two genes into dosing algorithms could lead to a safer anticoagulation therapy.

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Available abstract

Single nucleotide polymorphisms (SNPs) in genes encoding cytochrome P450 enzyme 2C9 (CYP2C9) and Vitamin K epoxide reductase subunit I (VKORC1) make a significant contribution to the inter-individual variability in the maintenance dose of vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon). Doses requirements in CYP2C9*2 and CYP2C9*3 heterozygotes are reduced by 8-16% and 20-36%, respectively. SNP g-1639a in VKORC1 is also associated with vitamin K antagonists dosage since heterozygotes ga and homozygotes aa require respectively 21-28% and 27-56% less warfarin or acenocoumarol than homozygotes gg. CYP2C9 and VKORC1 account for up to half the variability in vitamin K antagonists requirements and incorporating genotying data for these two genes into dosing algorithms could lead to a safer anticoagulation therapy.

Key concepts: VKORC1, Acenocoumarol, Phenprocoumon, CYP2C9, Vitamin K epoxide reductase, Warfarin, Single-nucleotide polymorphism, Pharmacology

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