[Pharmacogenetics of oral anticoagulants: individualized drug treatment for more efficacy and safety].
Oral anti-vitamin K (AVK) anticoagulants constitute the first cause of iatrogenic accidents in France because of narrow therapeutic index and bleeding risk. The wide interindividual variation in AVK response is partly genetically determined. The main enzyme responsible for the metabolism of AVK is the hepatic cytochrome P450 2C9 (CYP2C9). Vitamine K epoxide reductase complex subunit I (VKORC1) is a key enzyme in the vitamin K cycle, cofactor required for the activation of vitamin K-dependent clotting factors, and is the target enzyme of AVK inhibition. Genetic variations affecting both CYP2C9 and VKORC1 are associated with variability in drug response and may explain differences in dose requirements. Genotyping for CYP2C9 and VKORC1 variants before initiation of treatment may allow clinicians to develop dosing protocols and identify the patients at a higher risk for bleeding complications.
Loriot
Marie-Anne
MA
Inserm U-775, Université Paris-Descartes, 75006 Paris. Marie-Anne.Loriot@univ-paris5.fr
Beaune
Philippe
P
D000284:Administration, Oral; 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; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases
D000925:Anticoagulants; 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