Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel

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 acti...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology reports 2019-08, Vol.46 (4), p.4195-4199
Main Authors: Mirzaev, K. B., Samsonova, K. I., Potapov, P. P., Andreev, D. A., Grishina, E. A., Ryzhikova, K. A., Sychev, D. A.
Format: Article
Language:English
Subjects:
Acute Coronary Syndrome - drug therapy
Acute Coronary Syndrome - genetics
Acute coronary syndromes
Adult
Aged
Aged, 80 and over
Alleles
Animal Anatomy
Animal Biochemistry
Biomarkers, Pharmacological
Biomedical and Life Sciences
Blood Platelets - metabolism
Clopidogrel
Clopidogrel - pharmacology
Coronary Artery Disease - genetics
Cortisol
CYP3A protein
Cytochrome P-450 CYP3A - genetics
Cytochrome P-450 CYP3A - metabolism
Female
Gene frequency
Gene Frequency - genetics
Gene polymorphism
Genotype
Genotyping
High-performance liquid chromatography
Histology
Humans
Isoenzymes
Life Sciences
Male
Middle Aged
Morphology
Original Article
Phenotype
Phenotyping
Platelet aggregation
Platelet Aggregation - drug effects
Platelet Aggregation - genetics
Platelet Aggregation Inhibitors - metabolism
Platelet Aggregation Inhibitors - pharmacology
Polymorphism, Genetic - genetics
Statistical analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-019-04871-y