title: [Genetic and bioenvironmental factors associated with warfarin response in Colombian patients].
abstract: BACKGROUND
  Warfarin is an anticoagulant that is difficult to administer because of its narrow therapeutic margin and the numerous factors that influence patient response.
  
  
  OBJECTIVE
  Demographic, clinical and genetic variables were characterized to establish the appropriate maintenance dosages of warfarin.
  
  
  METHODS
  The Colombian patients consisted of 145 adults of both sexes. They were in stable anticoagulation status with international normalized ratio between 2 and 3 for at least two months, and without changes in the warfarin commercial preparation or in the dosage. After signing the informed consent, the following data was recorded for each volunteer: age, gender, weight, height, smoker status, co-morbidity, co-medication, International Normalized Ratio (INR), warfarin dose, and commercial brand. Each patient was typed for genes CYP2C9, VKORC1, CYP4F2 and PROC; for 59 patients, the serum levels of warfarin were quantified. The genotyping and the blood quantification were performed by mini-sequencing and HPLC methods, respectively.
  
  
  RESULTS
  Age, co-medication with enzymatic inhibitors (amiodarone, sertraline, fluoxetine) or inducers (phenytoin, carbamazepine), and the alleles rs1799853 (*2) and rs1057910 (*3) of the CYP2C9 gene, as well as rs9923231 of the VKORC1 gene were associated with warfarin dose required to achieve anticoagulation with INR of 2-3. These variables were included in a multiple linear regression model for predicting the optimum dose/week of warfarin. This resulted in an algorithm that explained 47.4% of the variability in the dose responses.
  
  
  CONCLUSIONS
  Clinical and pharmacogenetic variables provided a basis for improving the safety and effective dosage of warfarin; however, the use of a pharmacogenetic algorithm will require patient data obtained during clinical trials.
authors.affiliation: Facultad de Ciencias de la Salud, Universidad Tecnológica de Pereira, Colombia. caisaza@utp.edu.co
authors.forename: Carlos
authors.initials: C
authors.lastname: Isaza
authors.forename: Leonardo
authors.initials: L
authors.lastname: Beltrán
authors.forename: Julieta
authors.initials: J
authors.lastname: Henao
authors.forename: Gloria
authors.initials: G
authors.lastname: Porras
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pinzón
authors.forename: Alvaro
authors.initials: A
authors.lastname: Vallejos
authors.forename: Jorge
authors.initials: J
authors.lastname: Machado
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002986:Clinical Trials as Topic; D003105:Colombia; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004777:Environment; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D004791:Enzyme Inhibitors; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases