Characterization of a novel CYP2C9 mutation (1009C>A) detected in a warfarin-sensitive patient.

摘要: Warfarin is the most frequently prescribed anticoagulant for long-term treatment in clinic. Recent studies have shown that polymorphic alleles within CYP2C9, VKORC1, and CYP4F2 genes are related to warfarin dosage requirement. In this study, a novel non-synonymous mutation (1009C>A) CYP2C9 was detected warfarin-hypersensitive patient, while other two candidate were both found be homozygous wild-type alleles. The newly identified point results an amino acid substitution at position 337 of protein (P337T) has been designated as allele CYP2C9*58. When expressed insect cell microsomes, relative intrinsic clearance values CYP2C9.58 variant tolbutamide losartan quite similar those typical defective CYP2C9.3, whereas value diclofenac slightly higher than another CYP2C9.2. These data suggested when compared with CYP2C9.1, enzymatic activity allelic greatly reduced by 1009C>A mutation. If patients carrying take drugs metabolized their metabolic rate might slower carriers thus much more attention should paid clinical care.