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

Autor: Bačković Dragana, Ignjatović Svetlana, Rakićević Ljiljana, Kusić-Tišma Jelena, Radojković Dragica, Ćalija Branko, Strugarević Evgenija, Radak Đorđe, Kovač Mirjana
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Journal of Medical Biochemistry, Vol 35, Iss 1, Pp 26-33 (2016)
Druh dokumentu: article
ISSN: 1452-8258
1452-8266
00726524
Popis: 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.
Databáze: Directory of Open Access Journals
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