Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel
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The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37–91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)—CC, 4 (4.9%)—CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)—GG, 3 (3.7%)—AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46–26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.
KeywordsAcute coronary syndrome (ACS) Clopidogrel Pharmacogenetics CYP3A4*22 CYP3A5*3 Resistance High residual platelet reactivity (HRPR)
This study has been supported by the Grant Council of the President of the Russian Federation for state support of young Russian scientists (grant of the President of the Russian Federation for state support of young Russian scientists of candidates of Sciences—no. MK-2617.2018.7).
Moreover, the funding organizations played no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the report for publication. K.B., E.A., K.A., P.P. carried out the molecular genetic stadies; K.B. and K.I. wrote the manuscript; D.A. and D.A supervised the project.
Compliance with ethical standards
Conflict of interest
All of the authors declare that they have no conflict of interest.
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