Influence of Cyp2c19*2 Gene Variant on Therapeutic Response During Clopidogrel Treatment in Patients with Carotid Artery Stenosis.

Autor: Bačković D; University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia., Ignjatović S; University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia; Center for Medical Biochemistry, Clinical Center of Serbia., Rakićević L; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia., Kusić-Tišma J; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia., Radojković D; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia., Čalija B; Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia., Strugarević E; Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia., Radak Ð; Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia., Kovač M; Faculty of Medicine, University of Belgrade, Serbia; Blood Transfusion Institute of Serbia, Hemostasis Department, Belgrade, Serbia.
Jazyk: angličtina
Zdroj: Journal of medical biochemistry [J Med Biochem] 2016 Jan; Vol. 35 (1), pp. 26-33. Date of Electronic Publication: 2015 Dec 30.
DOI: 10.1515/jomb-2015-0009
Abstrakt: 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 of CYP2C19*2 loss-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*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant 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 the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 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 the CYP2C19*2 alleles 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 the CYP2C19*2 allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01).
Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
Competing Interests: The authors stated that they have no conflicts of interest regarding the publication of this article.
Databáze: MEDLINE
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