Gene polymorphism of CYP450 2C9 and VKORC1 in Chinese population and their relationships to the maintaining dosage of warfarin / 中华流行病学杂志

ABSTRACT

Objective To investigate the distribution of gene polymorphism of CYP450 2C9 and VKORC1-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations.Contribution of CYP2C9 and VKORC1 genotype to the maintenance doses on warfarin was also studied.Methods The genotype and allele frequencies were calculated and compared with those in other populations.One hundred and one patients with stable anticoagulation with warfarin under a target international normalized ratio(INR)of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage.Results CYP450 2C9~*3 + 1075C/A allele frequencies were:AA in 449 cases(92.2%),AC in 36 cases(7.4%)and CC in 2 cases(0.4%),respectively.VKORC1-1639A/G allele frequencies were AA in 415 cases(85.2%),GA in 72 cases(14.8%),but GG in no case(0.0%),respectively.When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose,the final equation was:ln(D)=0.346 + 0.017(weight)-0.376(CYP450 2C9~*3 + 1075C/A)+ 0.148(VKORC1-1639A/G)-0.002(age)(r=0.827,P=0.02).Conclusion There existed significant gene polymorphism CYP450 2C9~*3 + 1075C/A and VKORC1-1639A/G in the Chinese Han population.Both Gene polymorphisms of CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.