Genetic variation of VKORC1 and CYP4F2 genes related to warfarin maintenance dose in patients with myocardial infarction.

The aim of this study was to investigate whether the VKORC13 (rs7294/9041 G > A), VKORC14 (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 VKORC13 and VKORC14 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 VKORC12, CYP2C92 and CYP2C93 polymorphisms, gave no significant associations for neither VKORC13, VKORC14 nor CYP4F2 (1347 C > T). In conclusion, in patients with myocardial infarction, the individual contribution to warfarin dose requirements from VKORC13, VKORC14, and CYP4F2 (1347 C > T) polymorphisms was negligible. Our results indicate that pharmacogenetic testing for VKORC12, CYP2C92 and CYP2C93 is more informative regarding warfarin dose requirements than testing for VKORC13, VKORC14, and CYP4F2 (1347 C > T) polymorphisms.