山东医药2018，Vol.58Issue(10)：21-24,4.DOI:10.3969/j.issn.1002-266X.2018.10.006
昆明汉族人群VKORC1、CYP2C9基因多态性对华法林稳态剂量的影响及预测剂量模型的建立
Effects of VKORC1 and CYP2C9 gene polymorphisms in Kunming Han population on warfarin steady-state dose and establishment of predictive dose model
摘要
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.关键词
华法林/维生素K环氧化物还原酶复合体1/细胞色素P4502C9/基因多态性/下肢深静脉血栓/预测剂量模型/昆明市/汉族Key words
warfarin/vitamin K epoxide reductase complex 1/cytochrome P4502C9/gene polymorphisms/deep vein thrombosis/predictive dose model/Kunming/Han nationality分类
医药卫生引用本文复制引用
肖成,胡莹,王玉明,徐梦云,李婉澜,柳杰..昆明汉族人群VKORC1、CYP2C9基因多态性对华法林稳态剂量的影响及预测剂量模型的建立[J].山东医药,2018,58(10):21-24,4.基金项目
云南省卫生厅科学研究基金项目(2016NS246). （2016NS246）
