BACKGROUND Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfar...

Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early international normalized ratio (INR) values during warfarin initiation. We examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adj...

We report the first genome-wide association study (GWAS) whose sample size (1,053 Swedish subjects) is sufficiently powered to detect genome-wide significance (p<1.5 x 10(-7)) for polymorphisms that modestly alter therapeutic warfarin dose. The anticoagulant drug warfarin is widely prescribed for reducing the risk of stroke, thrombosis, pulmonary embolism, and coronary malfunction. However, Cau...

Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early international normalized ratio (INR) values during warfarin initiation. We examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adj...

AIMS Polymorphisms in CYP2C9 and VKORC1 influence patients' phenprocoumon (PHE) and acenocoumarol (ACE) dose requirements. To provide physicians with tools to estimate the patient's individual dose, we aimed to develop algorithms for PHE and ACE. METHODS AND RESULTS In two Dutch anticoagulation clinics, data on age, sex, height, weight, co-medication, coumarin derivative doses, and internatio...

The objective of this study was to assess the relative influence of VKORC1 and CYP2C9 genetic variants on several clinical outcomes related to warfarin treatment. We conducted a retrospective cohort analysis of 172 anticoagulation clinic patients followed from warfarin initiation. We assessed the following clinical outcomes: time to stable dose; time in, above, and below therapeutic range; the ...

Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 enzymes. The aim of this study was to investigate whether any of the common single nucleotide polymorphisms (SNPs) in the POR gene and its flanking intergenic sequences correlate with interindividual variations in the warfarin maintenance dose (which is determined partly by rates of warfarin m...

BACKGROUND Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses, but the role of these variants during initial anticoagulation is not clear. METHODS In 297 patients starting warfarin therapy, we asse...

BACKGROUND Emergency department (ED) patients with venous thromboembolism (VTE) are eventually treated with a standard dose of warfarin despite the fact that a number of patients are known to be sensitive to warfarin and may experience supra-therapeutic INRs and adverse bleeding events. Pharmacogenetics is an emerging field of medical practice that seeks to improve drug safety and efficacy in a...