title: Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage.
abstract: OBJECTIVE
  ORM1 is a plasma drug binding protein. Its polymorphism rs17650 (S>F) has been reported to be an important factor affecting the binding ability and effect of antiretroviral protease inhibitors. The aim of this study was to determine whether the ORM1 rs17650 polymorphism also influences warfarin therapy.
  
  
  METHODS
  A total of 191 Chinese patients with steady-dose warfarin therapy were enrolled in this study. The patients were studied for warfarin maintenance dose, the ORM1 rs17650 polymorphism, and two polymorphisms previously demonstrated to affect warfarin response [CYP2C9 rs1057910 (3) and VKORC1 rs7294 (-1639 G>A)].
  
  
  RESULTS
  Warfarin dose was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910 and ORM1 rs17650 polymorphisms. Patients carrying the wild-type of these three genes (n = 96) took a mean dose of 3.0 ± 1.1 mg warfarin, which was significantly higher than that taken by the 52 S patients (2.7 ± 0.7) and 11 S S patients (2.5 ± 0.6 mg) (p = 0.048).
  
  
  CONCLUSIONS
  We identified ORM1 as another polymorphic gene affecting warfarin dose requirements. ORM1 S carriers require lower maintenance doses to achieve and maintain an optimal level of anticoagulation.
authors.affiliation: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology of Central South University, Changsha, China. wang_liansheng@hotmail.com
authors.forename: Lian Sheng
authors.initials: LS
authors.lastname: Wang
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Shang
authors.forename: Shu Ya
authors.initials: SY
authors.lastname: Shi
authors.forename: Yan Qing
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.forename: Zhi Hua
authors.initials: ZH
authors.lastname: Guo
authors.forename: Yi Chen
authors.initials: YC
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Ying Zi
authors.initials: YZ
authors.lastname: Liu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Tan
authors.forename: Hong Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Hai He
authors.initials: HH
authors.lastname: Jiang
authors.forename: Hai Tang
authors.initials: HT
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D009961:Orosomucoid / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D009961:Orosomucoid; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases