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

Abstract

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.