title: Pharmacogenetic association study of warfarin safety endpoints in Puerto Ricans.
abstract: OBJECTIVE
  This study was intended to determine the incidence rate of warfarin-related adverse events (e.g., bleeding) in Puerto Ricans and whether a genetic association between warfarin pharmacogenes and any of these adverse events was observed over the initiation period (i.e., the first 90 days of therapy).
  
  
  METHODS
  We conducted an observational, retrospective cohort study of pharmacogenetic association in 122 warfarin-treated, male, Puerto Rican patients (69.9 +/- 9.6 years) from the Veterans Affair Caribbean Healthcare System (VACHS) who consented to participate. Genotyping was performed using the CYP2C9 and VKORC1 assays by Luminex. Event-free survival curves were estimated using the Kaplan-Meier method and analyzed by log-rank test. Cox regression models were constructed and hazard ratios (HR) calculated.
  
  
  RESULTS
  Carriers of functional CYP2C9 and VKORC1 polymorphisms demonstrated a higher incidence rate of multiple adverse events (i.e., 5.2 vs. 1.0 cases per 100 patient-months; RR = 4.8, p = 0.12) than did wild types. A significant association was observed between multiple adverse events and carrier status (HR = 2.5; 95% CI: 1.0-6.3, p = 0.04). However, no significant associations between genotypes and individual outcomes over the first 90 days of therapy were found.
  
  
  CONCLUSIONS
  The association of CYP2C9 and VKORC1 genotypes and risks for adverse events due to exposure to warfarin was examined for the first time in Puerto Ricans. Despite a lack of association with individual events in this study population, our findings revealed a potential utility of genotyping for the prevention of multiple adverse events during warfarin therapy.
authors.forename: Isa I
authors.initials: II
authors.lastname: Valentín
authors.forename: Giselle
authors.initials: G
authors.lastname: Rivera
authors.forename: Mariely
authors.initials: M
authors.lastname: Nieves-Plaza
authors.forename: Iadelisse
authors.initials: I
authors.lastname: Cruz
authors.forename: Jessica Y
authors.initials: JY
authors.lastname: Renta
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Cadilla
authors.forename: Juan F
authors.initials: JF
authors.lastname: Feliu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Seip
authors.forename: Gualberto
authors.initials: G
authors.lastname: Ruaño
authors.forename: Jorge
authors.initials: J
authors.lastname: Duconge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011647:Puerto Rico; D012189:Retrospective Studies; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin