Influence Of CYP2C9*3, VKORC1-1639G>A And CYP4F2rs2108622Genetic Polymorphisms On Warfarin Dose

[Objective] To investigate the influence of the cytochrome P450, family2, subfamily C, polypeptide9(CYP2C9*3), vitamin K epoxide reductasecomplex, subunit1(VKORC1-1639G>A), and cytochrome P450, family4,subfamilyF, polypeptide2(CYP4F2rs2108622) genetic polymorphisms onwarfarin dose in patients with heart valve replacement, search for reasonsof individual differences on warfarin dose, guide reasonable usage ofwarfarin.[Methods] Collected the patients,blood samples who were operated inthe Department of Cardiovascular Surgery of Fujian Provincial Hospitalfrom November2011to August2012. Using the method of Polymerase ChainReaction（PCR）-gene sequencing to detected133cases after valve surgerypatients of long-term oral warfarin CYP2C9*3, VKORC1-1639G> A and CYP4F2rs2108622genetic polymorphism, grouped according to genotype, comparedthe average dose of warfarin of different genotypes and discussed theeffect of gene mutation on warfarin dose.[Results] The frequencies of CYP2C9*3AA, AC, CC were127cases,6cases,0case, the average dose of warfarin were3.75mg/day,2.13mg/day,the difference was statistically significant (P <0.05). The frequenciesof VKORC1-1639G> A GG, GA, AA were3cases,32cases,98cases, the averagedose of warfarin were6.0mg/day and4.5mg/day,3.0mg/day, the differencewas statistically significant (P <0.05). The frequencies of CYP4F2rs2108622CC, CT, TT were67cases,59cases,7cases, the average warfarindose were3.0mg/day,3.75mg/day,4.5mg/day, the difference wasstatistically significant (P <0.05).[Conclusion] CYP2C9*3, VKORC1-1639G>A and CYP4F2rs2108622genetic polymorphisms were associated with the difference of individual warfarindose, and then established the multiple linear regression model: Y=5.361－1.341(CYP2C9*3)－1.425(VKORC1-1639G>A)+0.531(CYP4F2rs2108622)+0.051(weight)－0.428(gender). We found that the effects of CYP2C9*3,VKORC1-1639G>A and CYP4F2rs2108622on warfarin dose are respectively5%,34.1%and7.9%, it is visible that VKORC1-1639G>A has the maximumimpact on warfarin dose according to the multiple linear regression model.