Study on warfarin individual dosage model based on clinical factors and gene in Chinese Han population

Abstract

Abstract: AIM: To assess the effect of clinical factors and gene polymorphism on stable warfarin dosage in Chinese Han population,then and to establish a dose adjustment model for clinical individualized medication.METHODS: Based on the specified standard,203 patients after cardiac valve surgery and taking with stable warfarin dosage treatment in a hospital from January 2011 to October 2013 were enrolled in the study. As well,all the patients′CYP2C9^*3,VKORC1-1639G/A genetic polymorphisms were detected by PCR-RELP and sequencing technology. Effects of above-mentioned gene polymorphisms on the dose of warfarin combining with clinical characteristics of patients were analyzed and set up computation model by multiple stepwise regression analysis.RESULTS: There was no significant association between the sexgender,smoking status,drinking status and hypertension history with stable warfarin dosage (P＞0.05).The stable dose of warfarin was negatively correlated with age(r=-0.155,P=0.027) and positively correlated with body height and body weight of patients(r=0.166,0.190,P=0.009,0.003).There were statistically significance significant in the effect of CYP2C9^*3,VKORC1-1639G/A polymorphisms on the dose of warfarin (P＜0.01). A medication model D=2.855－1.173×CYP2C9(AC)＋0.020×W－0.024×A＋4.064×VKORC1(GG)＋1.486×VKORC1(GA) was obtained.CONCLUSION: It shows that age,body height,body weight and CYP2C9^*3,VKORC1-1639G/A genetic polymorphisms have influences on the stable dose of warfarin. Individualized medication of warfarin could be optimized and probably better the individualized medication of warfarin based on the model which needs to be furthermore verified in clinic.

Key words: Warfarin, gene polymorphism, cytochrome P4502C9, vitamin K epoxide reductase subunit 1, individualized dosage model

CLC Number:

R969.1

LIU Jun, LUAN Jia-jie, XU Wen-ke, ZHU Yan-hong, WANG Wei-ping, ZHANG Da-fa. Study on warfarin individual dosage model based on clinical factors and gene in Chinese Han population[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(3): 284-290.

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