Study On The Predictive Model Of Warfarin Individualized Treatment After Cardiac Valve Replacement

Objective : Study the effects of CYP2C9*2,CYP2C9*3,CYP4F2,GGCX,VKORC1-1173,VKORC1-1639 gene polymorphisms,to obtain the distribution of genotypes in Chinese Han population by experimental method.Study gene polymorphisms and the effects of demographic and clinical factors on the stabilized dose of warfarin after valve replacement,and to establish a prediction model of stable dose of warfarin,to achieve the purpose of individualized anticoagulant therapy.The Methods: From October 15,2012 to December 20,2014,226 patients with valve replacement,and regular administration of warfarin in March and above,INR to reach the target range,were enrolled in this study.Extract DNA,Primers were designed and amplified by polymerase chain reaction(PCR)And the endogenous gene was digested with specific endonuclease.The specific results were obtained by electrophoresis.The target DNA gene sequence was obtained.The patient’s dose,clinical data and demographic characteristics and the INR were tracked.Combined with or without bleeding,thrombosis,then,with application of statistical methods to calculate the genetic and non-genetic factors on the stability of warfarin dose size,we inferred warfarin stable dose prediction model after valve replacement.Results:(1)The distribution of VKORC-1639G>A genotype was: AA、AG、GG accounted for 88.3%,11.2% and 0.05% respectively,and the allele frequencies were 93.9% and 6.1% respectively.The genotype distribution of VKORC-1173 was:TT,TC and CC were 84.9%,14.9% and 0.05% respectively,and the allele frequencies were 93.9% and 6.1% respectively.The genotype distribution of CYP2C9 * 3 was: * 1 / * 1,* 1 / * 3,* 3 / * 3 accounted for 92%,8%,0%,respectively,allele frequencies were 96% and 4%;The frequencies of CYP2C9 * 2 were: * 1 / * 1,* 1 / * 2,* 2 / * 2 were 98.9% and 1.1% respectively,and the allele frequencies were 99.5% and 0.5% respectively.The frequencies of CYP4F2(rs2108622)were as follows: CC,CT and TT were 56.4% and 36.7% and 6.9% respectively,and the allele frequencies were 99.5% and 0.5% respectively.The genotype frequencies of GGCX(rs6738645)were: TT,GT and GG were 41.5%,50.0% and 8.5% respectively,the allele frequencies were 66.5% and 33.5%,respectively.(2)The predicted dose model of warfarin was obtained:Y = 2.131-1.816V1173+ 0.369 GGCX + 1.529BSA-0.013Age(Y is the stable dose of warfarin,unit is mg,VKORC1-1173 When the genotype is AA type,take 1,non-AA to take 0,when GGCX for the GT type 1,non-GT take 0,BSA unit is m2,Age unit is year)Conclusion: The stable dose of warfarin has no obvious relationship with the expression of CYP2C9 * 2,CYP2C9 * 3,CYP4F2 and VKORC1-1639,and was related to the body surface area,age,VKORC1-1173 and GGCX genotype.The AA genotype of VKORC1-1173 and age was negatively correlated with warfarin stable dose,while GT genotype of GGCX and BSA had a positive correlation with the stable dose of warfarin.And the effect of VKORC1 on warfarin dose was greater than that of GGCX.