Influence of VKORC1-1639G/A and CYP2C9 1061A/C Polymorphisms on Warfarin Dose

Objective To investigate the influence of VKORC1-1639 G/A and CYP2C9 1061 A/C polymorphisms on warfarin dose in Chinese patients of Han nationality.Methods PCR-RFLP technique was used to genotype the VKORC1-1639 G/A and CYP2C9 1061 A/C polymorphisms of 129 warfarin-treated patients.The mean warfarin doses used for the patients with different VKORC1 and CYP2C9 genotypes were compared.Results The frequencies of the VKORC1-1639 AA,AG,GG genotypes in the patient group were 74.4 %(96),23.3 %(30)and 2.3 %(3),respectively;allele frequencies were 86% for VKORC1-1639 A and 14 % for G;frequencies of the CYP2C9 1061 AA,AC,CC genotypes were 90.7 %(117),8.5 %(11)and 0.8(1),respectively;allele frequencies were 95% for CYP2C9 1061 A and 5% for C.There were no significant difference in genotype distribution of VKORC1-1639 and CYP2C9 1061 between the patients and the healthy controls(χ2=2.614,P=0.265;χ2=2.493,P=0.259,respectively).The mean warfarin dose differed significantly among the VKORC1 genotypes(P0.001);the patients carrying VKORC1-1639 AA genotype had a lower mean warfarin dose(1.444±0.282 mg/INR)compared with those carring AG genogype(1.629±0.258 mg/INR)(P=0.02),and the mean warfarin dose of the patients with AG genotype was lower than those with GG genotype[(2.031±0.087)mg/INR,P=0.017].The carriers of CYP2C9 1061 C allele(AC+CC)had a lower warfarin dose(1.328±0.185 mg/INR)than those with CYP2C9 1061 AA genotype[(1.518±0.299)mg/INR,P=0.032].Conclusion There might be an association between VKORC1-1639 G→A,CYP2C9 1061 A→C transformation and decreased warfarin dose and the major genotype of VKORC1-1639(AA)might account for the universally lower warfarin dosage used in Chinese Han population.