CYP2C9 and VKORC1 Polymorphisms Are Associated with Warfarin Anticoagulation-Dose Requirements

Objective:To investigate the quantitative influence of cytochrome P450 2C9(CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms on warfarin dose requirements. Methods:A total of 73 patients (in Nantong area) taking warfarin were enrolled in the study. PCR-RFLP technique was used to genotype the CYP2C9-1061A/C and VKORC1-1639G/A polymorphisms in these warfarin-treated patients. The mean warfarin doses used for the patients with different VKORC1 and CYP2C9 genotypes were compared. Results:The frequencies of the CYP2C9-1061 A/C AA, AC, CC genotypes were 80.8% (59), 16.4% (12) and 2.8% (2). The CYP2C9-1061 A/C was associated with the differences of weekly mean varfarin dose. The dose was(26.25±11.36) mg/week for AA genotype,(17.38±7.20) mg/week for AC genotype and (13.57± 7.10) mg/week for CC genoype (P 0.005). The frequencies of VKORC1-1639 G/A AA, GA, GG genotypes were 76.7%(56) , 19.2%(14) and 4.1%(3) in the patient group. The VKORC1-1639G/A was also associated with the differences of weekly mean varfarin dose. The dose was(24.75±11.68) mg/week for GG genotype,(16.67±7.46)mg/week for GA genotype and (12.46±7.42) mg/week for AA genoype (P 0.005). Conclusion: There are polymorphisms of VKORC1-1639 G/A and CYP2C9-1061 A/C in patients of Nantong Han nationality, and there is significant difference in weekly mean warfarin dosage between patients with different genotypes of the CYP2C9-1061A/C and VKORC1-1639G/A.