title: [Establishment and preliminary validation of warfarin maintenance dose algorithm in Chinese Han Population].
abstract: OBJECTIVE
  To establish an algorithm to predict the warfarin maintenance dose in Chinese Han population and validate the accuracy of this algorithm.
  
  
  METHODS
  A total of 488 Chinese Han patients, hospitalized in Fuwai hospital and had a stable dose of warfarin and a target international normalized ratio (INR) of 1.5 to 3.0, were recruited. Indications for warfarin use included prosthetic heart valve, atrial fibrillation and pulmonary embolism. These patients were divided into derivation group (n = 323) and validation group (n = 165) according to the enrollment time. A warfarin maintenance dose algorithm was established based on genetic information, demographic characteristics and concomitant medications by multiple linear regression analysis in derivation group. In the validation group, we evaluated the accuracy of our algorithm by comparing the predicted dose with the actual dose.
  
  
  RESULTS
  Our algorithm included VKORC1-1639G > A, CYP2C9*3 and CYP4F2 genotype, age, Body hight, body weight, amiodarone and digoxin use (R(2) = 0.652, P < 0.001) .In the validation group, the average predicted dose by our algorithm had no statistical difference with the actual dose [(3.51 ± 1.03) mg vs. (3.53 ± 1.41) mg, P = 0.779]. Our algorithm identified 100 out of 165 (60.6%) patients in the validation group, whose predicted dose of warfarin was within 20% of the actual dose, and predicted warfarin dose was underestimated in 17.6% (29/165) patients and overestimated in 21.8% (36/165) patients.
  
  
  CONCLUSIONS
  Our algorithm based on VKORC1, CYP2C9 and CYP4F2 polymorphisms can help to predict the warfarin maintenance dose in Chinese Han Population.
authors.affiliation: Key Laboratory of Clinical Trial Research of Cardiovascular Drugs, Ministry of Health, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lou
authors.forename: Lu
authors.initials: L
authors.lastname: Hua
authors.forename: Lulu
authors.initials: L
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Haiwen
authors.initials: H
authors.lastname: Yu
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Xu
authors.affiliation: Email: winterliucn@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Yishi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D044466:Asian People / Q000235:genetics; D002681:China; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases