title: Influence of Cyp2c19*2 Gene Variant on Therapeutic Response During Clopidogrel Treatment in Patients with Carotid Artery Stenosis.
abstract: BACKGROUND
  Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence ofCYP2C19*2loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis.
  
  
  METHODS
  One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission.CYP2C19*2genotyping was performed by TaqMan Assay. The influence ofCYP2C19*2variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA).
  
  
  RESULTS
  Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for theCYP2C19*2allele and 1 (0.9%) wasCYP2C19*2homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with theCYP2C19*2alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with theCYP2C19*2alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for theCYP2C19*2allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01).
  
  
  CONCLUSIONS
  TheCYP2C19*2loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
authors.affiliation: University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Bačković
authors.affiliation: University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia; Center for Medical Biochemistry, Clinical Center of Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ignjatović
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Rakićević
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Kusić-Tišma
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia.
authors.forename: Dragica
authors.initials: D
authors.lastname: Radojković
authors.affiliation: Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia.
authors.forename: Branko
authors.initials: B
authors.lastname: Čalija
authors.affiliation: Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia.
authors.forename: Evgenija
authors.initials: E
authors.lastname: Strugarević
authors.affiliation: Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Ðorđe
authors.initials: Ð
authors.lastname: Radak
authors.affiliation: Faculty of Medicine, University of Belgrade, Serbia; Blood Transfusion Institute of Serbia, Hemostasis Department, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kovač
keywords: CYP2C19*2; clopidogrel; platelet reactivity