Analysis of the association of the CYP2C19 variants with the effects of clopidogrel therapy in patients underwent to carotid endarterectomy

Abstract

Introduction. Despite proven clinical effect of clopidogrel, a considerable number of patients do not have an adequate response to this type of medication. Problems during therapy occur in the form of resistance, which is present in 11% of patients or bleeding that occurs in about 9% of patients. Pharmacogenomics studies demonstrated that variants of the CYP2C19 gene significantly influence the interindividual heterogenity of the clopidogrel response. The American Heart Association, US Food and Drug Administration and the European Medicines Agency, cite the CYP2C19 gene as a significant factor which influences patients response to clopidogrel. Further, it has been shown that the contribution of genetic and non-genetic factors affecting clopidogrel therapy may vary between patients from different populations, which justifies conducting population-specific studies. The aim. The aim of our study was to examine the significance of the CYP2C19*2 and the CYP2C19*17 variants in the individual response to clopidogrel, in Serbian patients. Methods. The study involved 108 patients with carotid artery stenosis who underwent endarterectomy and received clopidogrel for at least 30 days after the intervention. Also, 120 patients with myocardial infarction receiving clopidogrel after PCI (percutaneous coronary intervention) were included. Commercial tests were used for standard laboratory testing. Allelic discrimination was performed after Sanger sequencing. Results were analysed using statistical tests. Results. In patients undergoing endarterectomy CYP2C19*2 carriers had a higher risk for being clopidogrel low-responder in comparison with non-carriers (1.250, 95% CI 1.695–1.658, P<0.01). In the group of patients undergoing PCI, risk for reinfarction in patients who were carriers of CYP2C19*2 was higher compared to patients with wild type genotype (OR 5.355, 95% CI 0.955-31.08; P=0.038). Variant CYP2C19*17 showed no association with variations in response to clopidogrel therapy. Conclusion. The CYP2C19*2 variant shows significant association with a poor response to clopidogrel and it should be considered when planning therapy.