Effects of the rs2244613 polymorphism of the CES1 gene on the antiplatelet effect of the receptor P2Y12 blocker clopidogrel

Karin B. Mirzaev; Darya V. Osipova; Elena J. Kitaeva; Vladimir V. Shprakh; Sherzod P. Abdullaev; Denis A. Andreev; Robert B. Mumladze; Dmitriy A. Sychev

doi:10.1515/dmpt-2018-0039

Article

Effects of the rs2244613 polymorphism of the CES1 gene on the antiplatelet effect of the receptor P2Y12 blocker clopidogrel

Karin B. Mirzaev , Darya V. Osipova , Elena J. Kitaeva , Vladimir V. Shprakh , Sherzod P. Abdullaev , Denis A. Andreev , Robert B. Mumladze and Dmitriy A. Sychev

Published/Copyright: September 27, 2019

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From the journal Drug Metabolism and Personalized Therapy Volume 34 Issue 3

Abstract

Background

The aim of this study was to evaluate the association of the carriage of the rs2244613 polymorphism of the CES1 gene with clopidogrel resistance as well as to evaluate the effectiveness of antiplatelet therapy in the carriers of this marker who have had acute coronary syndrome (ACS). This study also analyzes the procedure of percutaneous coronary intervention and compares the rs2244613 carrier rate between patients with ACS and healthy participants.

Methods

The study involved 81 patients diagnosed with ACS and 136 conditionally healthy participants. The optical detection of platelet agglutination by VerifyNow was employed to measure residual platelet reactivity in patients with ACS. The rs2244613 polymorphism was determined using real-time polymerase chain reaction.

Results

According to the results, the AA genotype of the rs2244613 polymorphism of the CES1 gene was detected in 37 patients (45.6%), the CA genotype in 42 patients (51.8%) and the CC genotype in 2 patients (2.6%). The level of residual platelet reactivity in rs2244613 carriers was higher compared with patients who did not have this allelic variant: 183.23 PRU ± 37.24 vs. 154.3 PRU ± 60.36 (p = 0.01). The frequencies of the minor allele C were 28.4% and 28.3% in patients with ACS and healthy participants, respectively. The results of the linear statistical model PRU due to CES1 genotype were as follows: df = 1, F = 6.96, p = 0.01). The standardized beta was 0.285 (p = 0.01) and R² was 0.081. However, we also added CYP2C19*2 and *17 into the linear regression model. The results of the model were as follows: df = 3, F = 5.1, p = 0.003) and R² was 0.166.

Conclusions

We identified a statistically significant correlation between the carriage of the rs2244613 polymorphism of the CES1 gene and the level of residual platelet aggregation among patients with ACS and the procedure of percutaneous coronary intervention.

Keywords: acute coronary syndrome (ACS); antiplatelet therapy; CES1; clopidogrel; rs2244613

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved its submission.
Research funding: This work was supported by grants from the President of the Russian Federation Council for state support of young Russian scientists (the Russian President’s Grant for the State Support of Young Russian Scientist PhDs - № MK-2617.2018.7).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2018-11-18

Accepted: 2019-06-12

Published Online: 2019-09-27

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2018-0039

Keywords for this article

acute coronary syndrome (ACS); antiplatelet therapy; CES1; clopidogrel; rs2244613