title: Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration.
abstract: BACKGROUND
  The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population.
  
  
  METHODS
  We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133).
  
  
  RESULTS
  Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms.
  
  
  CONCLUSIONS
  Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available. Original submitted 26 November 2014; Revision submitted 9 April 2015.
authors.affiliation: Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil.
authors.forename: Paulo Caleb Junior Lima
authors.initials: PC
authors.lastname: Santos
authors.affiliation: Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil.
authors.forename: Leiliane Rodrigues
authors.initials: LR
authors.lastname: Marcatto
authors.affiliation: Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil.
authors.forename: Nubia Esteban
authors.initials: NE
authors.lastname: Duarte
authors.affiliation: Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil.
authors.forename: Renata Alonso
authors.initials: RA
authors.lastname: Gadi Soares
authors.affiliation: Clinical Laboratory, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Celia Maria
authors.initials: CM
authors.lastname: Cassaro Strunz
authors.affiliation: Clinical Cardiology Division, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Maurício
authors.initials: M
authors.lastname: Scanavacca
authors.affiliation: Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil.
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001938:Brazil; D002138:Calibration; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; VKORC; algorithm; warfarin