title: P-glycoprotein: a clue to vitamin K antagonist stabilization.
abstract: BACKGROUND
  Acenocoumarol is a vitamin K antagonist used in some European countries. As warfarin, this drug is characterized by a narrow therapeutic index and a large interindividual variability.
  
  
  OBJECTIVE
  The objective of this study was to assess the involvement of ABCB1 polymorphisms on acenocoumarol treatment.
  
  
  METHODS
  An observational cohort study was conducted to assess whether there is an association between the presence of the allelic variants of the ABCB1 gene coding for P-glycoprotein and acenocoumarol stabilization and daily doses during the first 35 days of treatment.
  
  
  RESULTS
  One hundred and fifteen patients met the inclusion criteria. The results of the clinical study showed that carriers of ABCB1 c.3435TT were more rapidly stabilized than wild-type patients (HR: 2.97, 95% CI: 1.23-7.18; p = 0.02). The same tendency was observed for the ABCB1 c.2677GT and 2677TT genotypes compared with ABCB1 c.2677GG. The ABCB1 c.2677TT genotype was also associated with a significant increase in doses of acenocoumarol (p = 0.03), the same tendency was observed with the ABCB1 c.3435TT genotype compared with the wild-type patients.
  
  
  CONCLUSIONS
  These data suggest that ABCB1 polymorphisms could be involved in the response to acenocoumarol treatment.
authors.affiliation: Division of Clinical Pharmacology & Toxicology, University Hospitals of Geneva, Switzerland.
authors.forename: Liliane
authors.initials: L
authors.lastname: Gschwind
authors.forename: Victoria
authors.initials: V
authors.lastname: Rollason
authors.forename: Françoise
authors.initials: F
authors.lastname: Boehlen
authors.forename: Michela
authors.initials: M
authors.lastname: Rebsamen
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Alain
authors.initials: A
authors.lastname: Matthey
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonnabry
authors.forename: Pierre
authors.initials: P
authors.lastname: Dayer
authors.forename: Jules Alexandre
authors.initials: JA
authors.lastname: Desmeules
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000235:genetics; D000074:Acenocoumarol / Q000008:administration & dosage / Q000627:therapeutic use*; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D013923:Thromboembolism / Q000517:prevention & control; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000925:Anticoagulants; D014812:Vitamin K; D000074:Acenocoumarol
keywords: ABCB1; P-glycoprotein; acenocoumarol; drug transporter; gene polymorphism; pharmacogenetics; vitamin K antagonists