Influence of CYP2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis

Journal of Medical Biochemistry

Kovač Mirjana¹  Radak Đorđe²  Ćalija Branko³  Strugarević Evgenija³  Ignjatović Svetlana⁴  Bačković Dragana⁵  Kusić-Tišma Jelena⁶  Radojković Dragica⁶  Rakićević Ljiljana⁶ 

[1] Blood Transfusion Institute of Serbia, Hemostasis Department, Belgrade;Institute for Cardiovascular Diseases Dedinje, Belgrade + University of Belgrade, Faculty of Medicine;Institute for Cardiovascular Diseases Dedinje, Belgrade;University of Belgrade, Faculty of Pharmacy, Belgrade + Clinical Center of Serbia, Center for Medical Biochemistry;University of Belgrade, Faculty of Pharmacy, Belgrade;University of Belgrade, Institute of Molecular Genetics and Genetic Engineering;

关键词: clopidogrel;    cyp2c19*2;    platelet reactivity;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 c Yp 2C 19*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 c Yp 2C 19*2 allele vs. wildtype (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.

【 授权许可】

Unknown