title: Pharmacogenetics aspects of oral anticoagulants therapy.
abstract: BACKGROUND
  Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the most commonly prescribed types of medications. They are characterized by narrow therapeutic indices and inter-individual or intra-individual variability in response to the treatment.
  
  
  OBJECTIVE
  to establish the influence of several genetic factors on VKA efficacy and adverse reactions.
  
  
  RESULTS
  The metabolism of VKA differs depending on their chemical structure: indandiones derivatives (fluindione) or coumarin derivatives (acenocoumarol, phenprocoumon or warfarin). They are mostly metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9 (CYP2C9), resulting in inactive products. The gene encoding CYP2C9 is polymorphic, its genetic variants being associated with differences in the enzymatic activity of CYP2C9. The most important in terms of their frequency in the general population are CYP2C9*2 and CYP2C9*3. Both alleles are associated with a marked decrease in CYP2C9 enzyme activity. VK epoxide reductase (VKOR) is an enzyme with an important role in VK metabolism. Various polymorphisms in the VKORC1 gene have been described. VKORC1*2 haplotype seems to be the most important in relation to the variability in response to VKA.
  
  
  CONCLUSIONS
  Various studies have shown a relationship between the genotype and the mean warfarin maintenance dosing: in patients carrying 2C9*1/*2 alleles, the dose is reduced by 18-40% in patients carrying 2C9*2/*2 alleles, by 21-49% in patients carrying 2C9*1/*3 alleles. The A allele of the c.-1639G>A polymorphism in the VKORC1 gene is associated with the need for a lower dose of acenocoumarol in patients on anticoagulant therapy.
  
  
  BACKGROUND
  SNP = Single Nucleotide Polymorphism, VKA = vitamin K antagonists, C1 - VKORC1 = vitamin K epoxide reductase complex subunit, INR = International Normalized Ratio.
authors: Department of Pharmacology, Toxicology and Clinical Pharmacology, "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca.
authors: F C
authors: FC
authors: Militaru
authors: Department of Pharmacology, Toxicology and Clinical Pharmacology, "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca.
authors: S C
authors: SC
authors: Vesa
authors: 5th Department of Surgery, Municipal Hospital of Cluj-Napoca, "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca.
authors: T R
authors: TR
authors: Pop
authors: Department of Pharmacology, Toxicology and Clinical Pharmacology, "Iuliu Haţieganu" University of Medicine and Pharmacy Cluj-Napoca.
authors: A D
authors: AD
authors: Buzoianu
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014812:Vitamin K / Q000037:antagonists & inhibitors; D064417:Vitamin K Epoxide Reductases / Q000235:genetics
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9 gene; VKORC1 gene; Vitamin K antagonists