The Study Of Warfarin Maintenance Dose Algorithm In Xinjiang Uyghur Population

Objectives:To explore the effect of VKORC1、CYP2C9 genetic polymorphism on warfarin maintenance dose variation in Xinjiang Uyghur patients and establish a warfarin maintenance dose algorithm for Xinjiang Uyghur patients with therapeutic window for international normalized ratio(INR) in 1.5-3.0 and validated the accuracy of this algorithm.Methods:(1)Part one a total of 120 Xinjiang Uyghur patients with taking warfarin were recruited at the department of Affiliated Traditional Chinese Medical Hospital in Xinjiang Medical University.Anticoagulation indication include prosthetic heart valves、atrial fibrillation、deep venous thrombosis、left ventricular thrombus and pulmonary embolism.All patients target INR in 1.5-3.0.Using PCR direct sequencing method to detected VKORC1 、 CYP2C9 gene polymorphism.We recorded all selected patients demographic characteristics、stable dose of warfarin 、other accompanied diseases and 、 concomitant medications and genetic test results.Applied statistical method to analyze the factors effecting warfarin maintenance dose(VKORC1 、 CYP2C9 gene polymorphism 、 demographic characteristics 、 accompanied diseases and concomitant medications).(2)Part two all patients enrolled were divided into derivation group(n=90)and validation group(n=30) according to the chronological order.In derivation group,we adopted multiple linear regression analysis to establish a warfarin maintenance dose algorithm.In the validation group,we using our algorithm to predicted the warfarin maintenance dose and evaluated the accuracy of our algorithm by comparing the predicted dose with actual dose.Compare our algorithm with IWPC recommended algorithm and Huang algorithm in Chinese Han population to validate the accuracy of our algorithm in validation group.Validate the dose accuracy in different indication of anticoagulant treatment.Results:(1)CYP2C9 and VKORC1 gene polymorphisms could explain56.3%warfarin maintain dose variation in Xinjiang Uyghur population,impact are bigger than demographic factors、concomitant medications and complications.(2)We establish a warfarin maintenance dose algorithm for the Xin Jiang Uyghur Population based on the information of derivation group patients:Dose=3.642+0.910×VKORC1-1173TC+1.774×VKORC1-1173CC-2.660×CYP2C9CC+0.991×smoke-0.021×age(yr),Our developed algorithm could explain 35.3% of variation in warfarin stable dose.(3)Validation result:in validation group,we have no found statistical significance between predicted dose and patients actual dose(3.05±0.89 VS 3.01±1.46),among them 50% of patients predicted dose in the ideal dose criteria,20% of the patients predicted dose on the low side,30%of patients predicted dose on the high side.46.7% of patients predicted dose was on the low side in IWPC algorithm,and only 33.3% of patients dose was in the ideal dose criteria.We have no found statistical significance between predicted dose of Huang algorithm and patients actual dose(p > 0.05),among them 40% of patients predicted dose was in the ideal dose criteria.70% of the valve replacement patients predicted dose was in the ideal dose criteria.Conclusion: 1.CYP2C9 and VKORC1 gene polymorphisms was the main factors for the effecting warfarin maintain dose in Xinjiang Uyghur population.2.Our algorithm can be use to predicting the maintenance dose of patients with valve replacement 、 atrial fibrillation 、 deep vein thrombosis 、 left ventricular thrombosis and pulmonary embolism.But because of the small sample size,need enlarging sample size to further improve the our algorithm.