| PurposeThe purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci(CYP2C9*3,VKORC1-1639G>A)on warfarin doses,to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3,VKORC1-1639G>A genotype,and to discuss the effects of 26 related gene polymorphisms on warfarin bleeding complications.MethodsThe study collects the data of patients in our hospital and other sub-centers which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model,and sequences 26 multigene sites in 451 patients.Based on the patient’s dosage,clinical data and demographic characteristics,the genetic and non-genetic effects on the initial dose and stable dose of warfarin is calculated by using statistical methods,and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression.At the same time,Logistic regression is used to analyze the principal factors contributing to the complications of warfarin bleeding.Results1.We have established a prediction model of initial dose of warfarin:initial dose of warfarin(mg/d)=[1.346+0.350×(VKORC1-1639G>A)-0.273×(CYP2C9*3)+0.245×(body surface area)-0.003×(age)-0.036×(amine iodone)+0.021×(sex)]~2.This model incorporates 7 factors and can explain 55.3%individualization differences of warfarin drug dose.2.We have established a prediction model of stable dose of warfarin:stable dose of warfarin(mg/d)=[1.336+0.299×(VKORC1-1639G>A)+0.480×(body surface area)-0.214×(CYP2C9*3)-0.074×(amine iodone)-0.003×(age)-0.077×(statins)-0.002×(height)]~2.This model incorporates 6 factors and can explain 42.4% individualization differences of warfarin drug dose.3.It shows that the polymorphism of the Apo E(rs429358)gene has an effect on the complications of haemorrhage in warfarin during normal INR.ConclusionThe genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study.The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice. |
