Genetic association between sensitivity to warfarin and expression of CYP2C9*3

摘要: Cytochrome P4502C9 (CYP2C9) is largely responsible for terminating the anticoagulant effect of racemic warfarin via hydroxylation pharmacologically more potent S-enantiomer to inactive metabolites. Mutations in CYP2C9 gene result expression three allelic variants, CYP2C9*1, CYP2C9*2 and CYP2C9*3. Both CYP2C9*3 exhibit altered catalytic properties vitro relative wild-type enzyme. In present study, a patient was genotyped who had proven unusually sensitive therapy could tolerate no than 0.5 mg drug/day. PCR-amplification exons 3 7 gene, followed by restriction digest or sequence analysis, showed that this individual homozygous addition, plasma enantiomer ratios urinary 7-hydroxywarfarin were determined chiral-phase high performance liquid chromotography order investigate whether either parameter might be diagnostic value place genotypic test. Control patients receiving 4-8 warfarin/day exhibited S:R 0.50 +/- 0.25:1, whereas on very low-dose an ratio 3.9:1. contrast, 4:1 same stereoselectivity as reported control patients. Therefore, associated with diminished clearance S-warfarin dangerously exacerbated therapeutic response normal doses drug. Analysis may serve useful alternative test genotyping genetic defect.