title: VKORC1 variant genotypes influence warfarin response in patients undergoing total joint arthroplasty: a pilot study.
abstract: Warfarin dosing algorithms do not account for genetic mutations that can affect anticoagulation response. We retrospectively assessed to what extent the VKORC1 variant genotype would alter the likelihood of being a hyperresponder or hyporesponder to warfarin in patients undergoing total joint arthroplasty. We used the international normalized ratio (INR) on the third postoperative day of 3.0 or greater to define warfarin hyperresponders and 1.07 or less to define hyporesponders. A control group of normal responders was identified. From a cohort of 1125 patients receiving warfarin thromboprophylaxis, we identified 30 free of predisposing factors that could affect warfarin response: 10 hyperresponders, eight hyporesponders, and 12 normal responders. Homozygous carriers of the VKORC1 mutant AA genotype were more likely (compared with carriers of GA or GG genotypes) to be hyperresponders (odds ratio, 7.5; 95% confidence interval, 1.04-54.1). Homozygous carriers of the GG (normal) genotype were more likely (compared with carriers of AA or GA genotypes) to be hyporesponders (odds ratio, 9; 95% confidence interval, 1.14-71). Preoperative screening for the VKORC-1 genotype could identify patients with a greater potential for being a hyperresponder or hyporesponder to warfarin. This may allow an adjusted pharmacogenetic-based warfarin dose to optimize anticoagulation, reducing postoperative risks of bleeding and thrombosis or embolism.
  
  
  METHODS
  Level III, diagnostic study.
authors.affiliation: Department of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. gonzaleza@hss.edu
authors.forename: Alejandro
authors.initials: A
authors.lastname: González Della Valle
authors.forename: Saurabh
authors.initials: S
authors.lastname: Khakharia
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Glueck
authors.forename: Nicole
authors.initials: N
authors.lastname: Taveras
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Robert N
authors.initials: RN
authors.lastname: Fontaine
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Salvati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases