title: [Effect of VKORC1 and CYP2C9 variants on dosage of oral anticoagulants in Chilean individuals].
abstract: BACKGROUND
  The dose of oral anticoagulants (OAC) shows great variability among patients. Pharmacogenetic studies have shown that common variants in genes CYP2C9 (*2 and *3) and VKORC1 (-1639G>A) are associated with lower requirements of OAC.
  
  
  OBJECTIVE
  To study the association between average maintenance doses of oral anticoagulant therapy required to maintain a stable INR and CYP2C9 and VKORC1 gene variants in Chilean adults.
  
  
  METHODS
  Prospective study of patients on anticoagulant treatment and with a stable international normalized ratio (INR) for prothrombin time for at least three months. Patients were classified as having high or low acenocoumarol or warfarin requirements. Peripheral blood DNA genotyping was performed by polymerase chain reaction and restriction fragment polymorphism or sequencing and electrophoresis.
  
  
  RESULTS
  The study included 185 patients, 125 on acenocoumarol and 60 on warfarin. Patients with VKORC1-1639A allele were more likely to require lower doses of both drugs than patients with the G allele (Odds ratio [OR] for acenocoumarol 9.06, and OR for warfarin = 18.7). There was no association between CYP2C9*2 and*3 and acenocoumarol or warfarin requirements.
  
  
  CONCLUSIONS
  There is an association between VKORC1-1639A variant and anticoagulant doses.
authors.forename: Felipe
authors.initials: F
authors.lastname: Benavides
authors.forename: Nicole
authors.initials: N
authors.lastname: Grossman
authors.forename: Helena
authors.initials: H
authors.lastname: Poggi
authors.forename: Elena
authors.initials: E
authors.lastname: Nieto
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertrán
authors.forename: Daniel
authors.initials: D
authors.lastname: Araos
authors.forename: Marcos
authors.initials: M
authors.lastname: Vásquez
authors.forename: Ignaz
authors.initials: I
authors.lastname: Ibarra
authors.forename: Felipe
authors.initials: F
authors.lastname: Cáceres
authors.forename: Karena
authors.initials: K
authors.lastname: Espinoza
authors.forename: Marcela
authors.initials: M
authors.lastname: Lagos
authors.forename: Marcel
authors.initials: M
authors.lastname: Lagos
authors.forename: Gabriela
authors.initials: G
authors.lastname: Repetto M
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D002677:Chile; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011517:Prothrombin Time; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000074:Acenocoumarol