Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol.
The 2C9*3 and 2C9*2 polymorphisms of cytochrome P-450 CYP2C9 are associated with hypersensitivity to warfarin and bleeding. The effect of these polymorphisms on sensitivity to acenocoumarol is unknown. Three groups of patients, with low, medium, or high acenocoumarol-dose requirements, were studied. Age influenced the acenocoumarol sensitivity. Bearing the 2C9*3 allele was associated with the need for a lower acenocoumarol dose (odds ratio [OR], 6.02; 95% confidence interval [CI], 1.50-24.18); 80% of carriers of the 2C9*3 allele required a low dose. The 2C9*2 allele was associated with a lower acenocoumarol-dose requirement (OR, 2.70; 95% CI, 1.11-6.58) because of a reduced risk of the need for a high acenocoumarol dose (4.8% of the patients in the high-dose group carried the 2C9*2 allele versus 34.1% and 30.2%, respectively, in the medium-dose and low-dose groups). Therefore, carriers of 2C9*3 may need a low initial loading dose of acenocoumarol. Because acenocoumarol sensitivity with the 2C9*2 variant does not seem to be clinically relevant, the drug could be an alternative to warfarin in 2C9*2 carriers.
Hermida
José
J
Hemostasis and Thrombosis Research Unit, School of Medicine, University of Navarra, Pamplona, Spain.
Zarza
José
J
Alberca
Ignacio
I
Montes
Ramón
R
López
María Luz
ML
Molina
Eva
E
Rocha
Eduardo
E
D000074:Acenocoumarol / Q000494:pharmacology*; D000483:Alleles; D000925:Anticoagulants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics*; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000187:drug effects / Q000235:genetics*; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; D017931:DNA Primers; D007527:Isoenzymes; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D000074:Acenocoumarol