The Clinical Study Of Influence Of CYP2C9 And VKORC1 Genetic Polymorphisms On Maintenance Warfarin Dose In Pulmonary Embolism Patients

Objective:To evaluate the effect of cytochrome P-450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genetic polymorphisms on maintenance warfarin dose in pulmonary embolism patients.Method:1、Collected 46 pulmonary embolism patients in respiratory medicine of The First Affiliated Hospital of Kunming Medical University from January 2014 to December 2014. The genetic polymorphisms of CYP2C9(1075A>C)and VKORC1(-1639G>A) were detected by using direct sequencing method.2、Recorded the clinical data including age, gender, weight and height of the patients. According to international standard ratio (INR) adjust the dose of warfarin, and record warfarin maintenance dosage.3、Analysis with warfarin maintenance dosage if there is a correlation between gene polymorphism of CYP2C9(1075A>C)and VKORC1 (-1639G>A)and clinical factors by using statistical methods. Set up a warfarin maintenance dosage model by using the multiple regression method.Result:1、VKORC1 (-1639G>A) gene:38 cases of AA type, warfarin dose 2.93±0.55mg/d, 8 cases of GA type, warfarin dose 4.78±0.39mg/d. The warfarin dose of AA type is lower than GA type. Comparison between groups was statistically difference (P<0.001)2、CYP2C9 (1075A>C) gene:44 cases of AA type, warfarin dose 3.26±0.84mg/d,2 cases of AC type, warfarin dose 2.00±0.72mg/d. The warfarin dose of AC type is lower than the AA type. Comparison between groups was statistically difference (P<0.05)3、single factor regression analysis prompts:The influence of age and VKORC1 (-1639G>A) gene polymorphism with warfarin maintenance dosage was statistically significant, can explain 13.6% and 64.3% of individual difference of warfarin dose in pulmonary embolism patients. The gender, height, weight and CYP2C9 gene polymorphism in pulmonary embolism patients effect of warfarin maintenance dosage has no statistical significance (P>0.05).4、By gender, age, height, weight, CYP2C9 and VKORC1 as independent variables, and warfarin as the dependent variable to establish the forecast model of maintenance dose of warfarin:dose (mg)=1.940-0.012×age+1.736×VKORC1. This model can explain about 69.1% warfarin maintenance dosage in pulmonary embolism patients.Conclusion:Detection of CYP2C9 and VKORC1 polymorphisms may have clinical significance to guide the individualized warfarin dosage in pulmonary embolism patients.