Abstract
The aim of this study was to investigate whether the VKORC1*3 (rs7294/9041 G > A), VKORC1*4 (rs17708472/6009 C > T), and CYP4F2 (rs2108622/1347 C > T) polymorphisms were associated with elevated warfarin maintenance dose requirements in patients with myocardial infarction (n = 105) from the Warfarin Aspirin Reinfarction Study (WARIS-II). We found significant associations between elevated warfarin dose requirements and VKORC1*3 and VKORC1*4 polymorphisms (P = .001 and P = .004, resp.), whereas CYP4F2 (1347 C > T) showed a weak association on higher warfarin dose requirements (P = .09). However, analysing these variant alleles in a regression analysis together with our previously reported data on VKORC1*2, CYP2C9*2 and CYP2C9*3 polymorphisms, gave no significant associations for neither VKORC1*3, VKORC1*4 nor CYP4F2 (1347 C > T). In conclusion, in patients with myocardial infarction, the individual contribution to warfarin dose requirements from VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms was negligible. Our results indicate that pharmacogenetic testing for VKORC1*2, CYP2C9*2 and CYP2C9*3 is more informative regarding warfarin dose requirements than testing for VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms.
Highlights
Warfarin has an established role in secondary prevention of atherothrombotic disease, reducing new thromboembolic events [1]
The aim of this study was to investigate whether the VKORC1∗3, VKORC1∗4, and CYP4F2 polymorphisms were associated with elevated warfarin maintenance dose requirements in patients with myocardial infarction (n = 105) from the Warfarin Aspirin Reinfarction Study (WARIS-II)
Our results indicate that pharmacogenetic testing for VKORC1∗2, CYP2C9∗2 and CYP2C9∗3 is more informative regarding warfarin dose requirements than testing for VKORC1∗3, VKORC1∗4, and CYP4F2 (1347 C > T) polymorphisms
Summary
Warfarin has an established role in secondary prevention of atherothrombotic disease, reducing new thromboembolic events [1]. An increasing number of genetic variations affecting warfarin pharmacokinetics and/or pharmacodynamics have recently been reported to have major impact on dosage requirements, that is, polymorphisms in the CYP2C9, VKORC1, and CYP4F2 genes [2,3,4,5,6,7]. We have found VKORC1∗2 to account for 24.5%, and the combination of CYP2C9∗2 and CYP2C9∗3 (rs1799853 and rs1057910) to account for 7.2% of the warfarin maintenance dose variation in patients from the Warfarin Aspirin Reinfarction Study (WARIS-II) [9]. We aimed to study whether the highdose polymorphisms VKORC1∗3, VKORC1∗4, and CYP4F2 (rs2108622/1347 C > T) were associated with elevation in warfarin maintenance dose requirements in the same patient group
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