title: Genotype and risk of major bleeding during warfarin treatment.
abstract: OBJECTIVE
  To determine whether genetic variants associated with warfarin dose variability were associated with increased risk of major bleeding during warfarin therapy.
  
  
  METHODS
  Using Vanderbilt's DNA biobank we compared the prevalence of CYP2C9, VKORC1 and CYP4F2 variants in 250 cases with major bleeding and 259 controls during warfarin therapy.
  
  
  RESULTS
  CYP2C9*3 was the only allele that differed significantly among cases (14.2%) and controls (7.8%; p = 0.022). In the 214 (85.6%) cases with a major bleed 30 or more days after warfarin initiation, CYP2C9*3 was the only variant associated with bleeding (adjusted odds ratio: 2.05; 95% CI: 1.04, 4.04).
  
  
  CONCLUSIONS
  The CYP2C9*3 allele may double the risk of major bleeding among patients taking warfarin for 30 or more days.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Vivian K
authors.initials: VK
authors.lastname: Kawai
authors.forename: Andrew
authors.initials: A
authors.lastname: Cunningham
authors.forename: Susan I
authors.initials: SI
authors.lastname: Vear
authors.forename: Sara L
authors.initials: SL
authors.lastname: Van Driest
authors.forename: Abimbola
authors.initials: A
authors.lastname: Oginni
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.forename: Christian
authors.initials: C
authors.lastname: Shaffer
authors.forename: Erica
authors.initials: E
authors.lastname: Bowton
authors.forename: Brian F
authors.initials: BF
authors.lastname: Gage
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Ray
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; CYP4F2; VKORC1; pharmacogenetics; risk of major bleeding; warfarin