title: Genetic characterization of warfarin sensitivity in a population of cardiovascular patients on chronic anticoagulation.
abstract: BACKGROUND
  Genetic factors account for 35-40% of the interindividual variation observed in response to warfarin. The most important genes involved are CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex subunit 1).
  
  
  OBJECTIVE
  To determine the prevalence of the different genotypes influencing response to oral anticoagulants in a population of cardiovascular patients on chronic anticoagulation and to investigate the correlation between genotype and the warfarin dose required for optimal anticoagulation.
  
  
  METHODS
  A total of 91 chronically anticoagulated consecutive patients were genotyped for CYP2C9 and VKORC1, using PCR and reverse hybridization.
  
  
  RESULTS
  Of the 91 patients, 57.1% were male and mean age was 67.4 +/- 13.1 years. most frequent indication for warf was atrial fibrillation (56.8%). We analyzed the prevalence of the different CYP2C9 and VKORC1 genotypes in this population and found that the warfarin doses required to maintain patients at their desired anticoagulation target were significantly different among carriers of the different genotypes.
  
  
  CONCLUSIONS
  Our study highlights the importance of genetic study in the clinical management of patients on chronic anticoagulation, increasing the safety and efficacy of warfarin therapy.
authors.affiliation: Serviço de Cardiologia dos Hospitals da Universidade de Coimbra, Coimbra, Portugal. elisabetejorge@gmail.com
authors.forename: Elisabete
authors.initials: E
authors.lastname: Jorge
authors.forename: João Mariano
authors.initials: JM
authors.lastname: Pêgo
authors.forename: Rui
authors.initials: R
authors.lastname: Baptista
authors.forename: Margarida
authors.initials: M
authors.lastname: Lourenço
authors.forename: Isabel
authors.initials: I
authors.lastname: Marques
authors.forename: Ana
authors.initials: A
authors.lastname: Correia
authors.forename: Pedro
authors.initials: P
authors.lastname: Monteiro
authors.forename: Ferrer
authors.initials: F
authors.lastname: Antunes
authors.forename: Luís A
authors.initials: LA
authors.lastname: Providência
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases