engleski

Cytochrome P450 - CYP2C9 Genotyping in Warfarin Drug Therapy Optimization

S&#8211; warfarin is an anticoagulant therapy drug and its often unpredictable dose response results at least in part due to genetic differences in CYP2C9 enzyme metabolic capacity. Besides wild type- CYP2C9*1, there are mutant alleles CYP2C9*2 and CYP2C9*3 that in homozygotes code enzymes with activities of only 16-20% and 5% of total wild type activity, respectively. Our aim was to investigate the possibility of warfarin dosage prediction by CYP2C9 polymorphism genotyping. We genotyped 181 patients (43.6 % males, mean age 60.2 ; SD=14.5) by PCR-RFLP method as reported by Nasu K. et al., 1997. Patients were receiving warfarin in doses needed for maintaining prothrombin time within INR range 1.5-2.5. Results showed significantly higher warfarin mean daily dose (DD) among 104 wild type homozygous patients (DD=4.4mg ; SD=1.9) compared to 77 patients with at least one mutated allele (DD= 3.7mg ; SD 1.7, p=0.010) and 10 patients with both mutant alleles (DD=2.6mg ; SD=1.4, p=0.004). Patients were also divided into groups according to warfarin median daily dose: among DD<4.1mg group (90 patients), we found 71% wild type (1*), and 29% mutated (2* and 3*) alleles. These 2* and 3* allelic frequencies were significantly higher (p=0.027) than in DD>4.1mg group (91 patients) (81% wild type (1*), and 19% mutated (2* and 3*) alleles). Genotype frequencies did not differ significantly. Results of our investigation are concordant to other author's findings and suggest a relationship of CYP2C9 defective alleles with lower warfarin doses. Therefore, CYP2C9 genotyping could be of predicting and optimizing importance in anticoagulant drug therapy.

CYP2C9; warfarin; anticoagulant therapy

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