title: Prevalence of genetic polymorphisms of CYP2C9 and VKORC1 - implications for warfarin management and outcome in Croatian patients with acute stroke.
abstract: BACKGROUND
  Data on the prevalence of CYP2C9 and VKORC1 genes and their influence on anticoagulant effect and warfarin dose in stroke patients are scarce. The aim of this study was to determine the occurrence and significance of these gene polymorphisms and to establish pharmacogenetic algorithm to estimate the dose of introduction. Also, the goal was to determine tailored safety and intensity of anticoagulation response depending on the allelic variants and their impact on the clinical outcome in acute stroke patients in Croatia.
  
  
  METHODS
  A total of 106 consented acute stroke patients were tested for CYP2C9 2, 3 and VKORC1 1173C>T gene polymorphisms. We estimated the dose of introduction and monitored anticoagulant effect obtained by INR values, time to reach stable dose, stable maintenance dose, time spent within the therapeutic/supratherapeutic INR range, occurrence of dosage side effects and clinical outcome depending on genotypes.
  
  
  RESULTS
  We found that 83% of stroke patients in our study were carriers of multiple allelic variants. The predicted initial dose correlated with the stable warfarin maintenance dose (p=0.0311) and we correctly estimated the dose for 81.5% of 61.3% of study patients who required higher/lower doses than average. Warfarin dosage complications were slightly more frequent among the carriers of CYP2C9 2, 3 compared to the carriers of VKORC1 1173T alleles (68. 9% versus 62.5%), but their occurrence did not affect the final clinical outcome.
  
  
  CONCLUSIONS
  Our data indicated rapid and safe anticoagulation achieved by using pharmacogenetically-predicted warfarin dose in high-risk acute stroke patients without increasing the risk of warfarin dosage complications in an elderly population.
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia. Electronic address: ssupe2@hotmail.com.
authors: Svjetlana
authors: S
authors: Supe
authors: Clinical Institute of Laboratory Diagnosis, Zagreb University Hospital Center, Department of Pharmacology, Zagreb, Croatia; University of Zagreb, School of Medicine, Croatia.
authors: Nada
authors: N
authors: Božina
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors: Vesna
authors: V
authors: Matijević
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors: Antonela
authors: A
authors: Bazina
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors: Antonija
authors: A
authors: Mišmaš
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors: Josip
authors: J
authors: Ljevak
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia.
authors: Domagoj
authors: D
authors: Alvir
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia; University of Zagreb, School of Medicine, Croatia.
authors: Mario
authors: M
authors: Habek
authors: Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia; University of Zagreb, School of Medicine, Croatia.
authors: Zdravka
authors: Z
authors: Poljaković
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D017523:Croatia / Q000453:epidemiology; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods; D008297:Male; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D018709:Statistics, Nonparametric; D020521:Stroke / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; Genetic polymorphism; Stroke; VKORC1; Warfarin