[Oral anticoagulation and pharmacogenetics: importance in the clinical setting].
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.
Benusiglio
Patrick R
PR
Service de médecine interne générale, HUG, 1211 Genève 14. patrick.benusiglio@hcuge.ch
Desmeules
Jules
J
de Moerloose
Philippe
P
Dayer
Pierre
P
D000925:Anticoagulants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D014812:Vitamin K / Q000037:antagonists & inhibitors; D064417:Vitamin K Epoxide Reductases
D000925:Anticoagulants; D014812:Vitamin K; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases