title: VKORC1 gene polymorphisms and adverse events in Croatian patients on warfarin therapy.
abstract: OBJECTIVE
  The objective was to determine the impact of VKORC1 polymorphisms on warfarin anticoagulant therapy (stable warfarin maintenance dose, time required to reach therapeutic dose and time spent in therapeutic range) and its adverse events (overanticoagulation and bleeding events, time to first overanticoagulation or bleeding event, and therapy for bleeding events) in Croatian patients.
  
  
  METHODS
  Blood samples were collected from 186 patients on stable warfarin therapy.
  
  
  METHODS
  VKORC1 1173C>T and VKORC1 â1639G>A gene polymorphisms were analyzed using real-time PCR. Prothrombin time international normalized ratio (INR) values were determined and overanticoagulation as well as bleeding events were recorded.
  
  
  RESULTS
  Both tested VKORC1 gene polymorphisms (VKORC1 1173C>T and VKORC1 -1639G>A) were in perfect linkage disequilibrium. Genotype analysis showed that 33.9% of patients were homozygous for wild-type, 46.8% were heterozygous and 19.4% were homozygous for the variant allele. We have found a statistically significant difference between variantallele carriers and wild-type patients in stable warfarin maintenance dose (p<0.001) and incidence of bleeding events (p=0.040). Patients homozygous for variant-allele were more likely to experience an overanticoagulation event in the first 30 days of therapy (p=0.040).
  
  
  CONCLUSIONS
  Our study showed that VKORC1 1173C>T and VKORC1 -1639G>A gene polymorphisms are associated with stable warfarin maintenance dose and adverse events of warfarin therapy.
authors.forename: Dario
authors.initials: D
authors.lastname: Mandic
authors.forename: Nada
authors.initials: N
authors.lastname: Bozina
authors.forename: Sanja
authors.initials: S
authors.lastname: Mandic
authors.forename: Marina
authors.initials: M
authors.lastname: Samardzija
authors.forename: Andrea
authors.initials: A
authors.lastname: Milostic-Srb
authors.forename: Lada
authors.initials: L
authors.lastname: Rumora
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D017523:Croatia; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019934:International Normalized Ratio; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011517:Prothrombin Time; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases / Q000235:genetics* / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases