title: Pharmacogenetics of coumarin anticoagulants in Brazilians.
abstract: BACKGROUND
  Coumarin vitamin K antagonists are the mainstay of anticoagulant therapy in atrial fibrillation, prosthetic heart valves and thromboembolic conditions. Concerns with these drugs include large inter-individual variability in dose requirements, narrow therapeutic index and need to monitor prothrombin time repeatedly.
  
  
  METHODS
  Pharmacogenetic studies and dosing algorithms for warfarin and phenprocoumon.
  
  
  CONCLUSIONS
  Gene candidate studies in Brazilian patients verified consistently the association of warfarin and pheprocoumon stable dose requirements with CYP2C9 and VKORC1 polymorphisms, and minor or no influence of other pharmacogenes (e.g., CYP4F2 and F7). The predictive power of warfarin and phenprocoumon dosing algorithms developed for Brazilians compares favorably with those reported for other populations. A warfarin dosing algorithm derived for an admixed cohort performed equally well in self-reported White and Black patients, in marked contrast with the considerably poorer performance of other warfarin algorithms in patients of African descent compared to those of European ancestry. This discrepancy is ascribed to the extensive European/African admixture among Brazilians. Prospective studies of clinical utility of coumarin dosing algorithms, in the context of the Brazilian Public Health System, would represent an important counterpart to recently published trials in European and North American cohorts with predominant or exclusive European ancestry.
authors.affiliation: Instituto Nacional de Câncer, Pharmacology Division , Rua André Cavalcanti 37, Rio de Janeiro, CEP 20231-050, RJ , Brazil +5521 3207 6502 ; kurtz@inca.gov.br.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Suarez-Kurtz
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Botton
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology*; D001938:Brazil / Q000208:ethnology; D003374:Coumarins / Q000009:adverse effects / Q000494:pharmacology*; D005006:Ethnicity / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D000925:Anticoagulants; D003374:Coumarins; C030123:coumarin
keywords: Brazil; CYP2C9; CYP4F2; VKORC1; coumarin; dosing algorithms; pharmacogenetic polymorphisms; phenprocoumon; warfarin