Study On Steady-state Dose Of Warfarin In Patients With Deep Vein Thrombosis Of Lower Extremities And The Establishment Of Predictive Dose Models

Objectives:1.To investigate whether the vitamin K epoxide reductase complex 1(VKORC1)gene and the cytochrome P4502C9(CYP2C9)gene polymorphism exist in patients with lower extremity deep venous thrombosis of Kunming Han population.2.Based on the study of VKORC1 and CYP2C9 gene polymorphisms,to investigate its effect on the steady-state dose of warfarin in patients with lower extremity deep venous thrombosis.3.Warfarin’s predicted dose model was established to accurately assess the dose of warfarin in patients with deep venous thrombosis of the lower extremities in the Kunming Han population.Methods:1.A total of 162 patients with deep venous thrombosis of the lower extremities treated with warfarin anticoagulant therapy were selected to detect the polymorphisms of VKORC1 and CYP2C9*3 genes in patients’ blood by amplification-blocking mutation system-polymerase chain reaction(ARMS-PCR).2.The patient’s age,gender,height,body mass,body mass index(BMI),international standard ratio(INR)were recorded.3.The correlation analysis was used to analyze the relationship between clinical data and individual doses of warfarin,and the patient’s VKORC1 and CYP2C9 genotypes,age,sex,body weight,height,INR,and application of warfarin were combined to perform multiple stepwise regression analysis to obtain predicted doses model.4.In addition,20 patients were selected and observed for efficacy using the doses recommended by the predicted dose model.Results:1.Of the 162 patients enrolled,the AA,AG,and GG genotypes of VKORC1-1639 G>A were 138(85.19%),22(13.58%),and 2(1.23%),respectively.The warfarin steady-state dose of AA was lower than that of AG and GG.2.The AA and AC genotypes of CYP2C9*3(1075A>C)in 162 patients were 151(93.21%)and 11(6.79%)respectively.Among them,the warfarin steady-state dose of AC was lower than that of AA.3.VKORC1-1639G>A and CYP2C9*3 genotype distribution and allele frequencies are in line with the frequency distribution of Hardy-weinberg genetic equilibrium law(P>0.05).4.Correlation analysis showed that age,body mass,VKORC1 and CYP2C9 gene polymorphisms were related to individual warfarin doses.5.The predictive dose model:Warfarin dosage=3.401-0.027×age+0.015×body weight-0.312×CYP2C9+0.979×(VKORC1-X1)+0.64×(VKORC1-X2),r=0.816.6.The use of predictive dose model recommended dose was effective,and there was no occurrence of adverse events.Conclusions:1.There are VKORC1 and CYP2C9 gene polymorphisms in Kunming Han Population.2.There is a significant correlation between the predicted dose in the selected patient and the actual steady-state dose.3.Application of the established model of predicted dose could more accurately assess the dose of warfarin.4.The experimental dose can be administered using the dose recommended by the predicted dose model.