title: [Impact of six genetic polymorphisms on Warfarin maintenance dose variation in Chinese Han population].
abstract: OBJECTIVE
  To evaluate the effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms on Warfarin maintenance dose variation in Chinese Han Population.
  
  
  METHODS
  Four hundred eighty-eight patients with prosthetic heart valves, atrial fibrillation or pulmonary thromboembolism and achieved stable Warfarin dose were enrolled. TaqMan probe or direct sequencing were used to genotype Y9VKORC1, CYP2C9, GGCX, EPHX1 and CYP4F2 gene polymorphisms. Demographic characteristics, stable therapeutic dose of Warfarin and concomitant medications were collected for all patients. The effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms, demographic characteristics and concomitant medications on Warfarin daily maintenance dose were analyzed with statistical method.
  
  
  RESULTS
  VKORC1 and CYP2C9 gene polymorphisms could explain more than 50% Warfarin maintenance dose variation in recruited patients, while CYP4F2 gene polymorphisms could only explain 1%. GGCX, PROC and EPHX1 gene polymorphisms had no impact no Warfarin maintenance dose. VKORC1 and CYP2C9 gene polymorphisms have a greater impact on Warfarin maintenance dose compared with demographic characteristics and concomitant medications.
  
  
  CONCLUSIONS
  VKORC1 and CYP2C9 gene polymorphisms have a significant impact on Warfarin maintenance dose in Chinese Han population.
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs of Ministry of Health, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, P.R. China. Email: winterliucn@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lou
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: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Haiwen
authors.initials: H
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Yishi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011486:Protein C / Q000235:genetics; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D011486:Protein C; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human