Effects of VKORC1 and CYP2C9 gene polymorphisms in Kunming Han population on warfarin steady-state dose and establishment of predictive dose model
XIAO Cheng
HU Ying
WANG Yuming
XU Mengyun
LI Wanlan
LIU Jie
Abstract：Objective To study the effect of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P4502C9 (CYP2C9) gene polymorphisms in Kunming Han population on steady-state dose of warfarin and to establish a predictive dose model. Methods Totally 162 blood samples from patients with deep venous thrombosis of lower extremity treated with warfarin anticoagulation were enrolled. The amplification block mutant system-polymerase chain reaction technology was used to detect the gene polymorphisms of VKORC1 and CYP2C9. The patients' age,sex,height,body weight, international standard ratio (INR) and the genotypes of VKORC1 and CYP2C9 were recorded. Pearson correlation analysis was used to screen the factors related to steady-state dose of warfarin. The multiple stepwise regression analysis of VKORC1 and CYP2C9 genotypes,age,sex,body weight,height,INR,and warfarin status in patients was used to predict the dose model. In addition,20 patients were selected to observe the occurrence of hemorrhagic events after using warfarin dosage recommended by the predicted dose model. Results During 162 cases of patients,there were 151 cases of CYP2C9 AA and 11 cases of CYP2C9 AC; among them,the warfarin recommended dose (combined amiodarone and non-amiodarone) of genotype AC was lower than that of genotype AA. The AA,AG,and GG types of VKORC1 were found in 138 cases,22 cases,and 2 cases,respectively; among them,the warfarin recommended dose (combined amiodarone and non-amiodarone) of AA type was significantly lower than that of the AG and GG types. The age,body weight,VKORC1,and CYP2C9 gene polymorphisms were related to the steady-dose of warfarin,but the height,BMI,and INR were not. The predictive dose model: Dose = 3.401 - 0.027 × Age + 0.015 × Weight - 0.312 × CYP2C9 + 0.979 × (VKORC1 - X1) + 0.64 ×(VKORC1 - X2),R2 = 0.816. Twenty patients using the predicted dose model did not have bleeding during the follow-up period. Conclusions There are VKORC1 and CYP2C9 gene polymorphisms in the Han population of Kunming. The gene polymorphisms of VKORC1 and CYP2C9 have a certain influence on steady-state dose of warfarin. We establish the warfarin predictive dose model and the established dose model can be used to accurately guide the medication of warfarin.
Keywords：warfarinvitamin K epoxide reductase complex 1cytochrome P4502C9gene polymorphismsdeep vein thrombosispredictive dose modelKunmingHan nationality
Publication Date：2018-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 21-24 )