Balkan Journal of Medical Genetics

CO-EXISTENCE OF CYP2C19*1/*2 AND ABCB1C.3435 CT GENOTYPE HAS A POTENTIAL IMPACT ON CLINICAL OUTCOME IN CAD PATIENTS TREATED WITH CLOPIDOGREL
Nestorovska KA, Naumovska Z, Staninova Stojovska M, Sterjev Z, Dimovski A, Suturkova Lj
*Corresponding Author: Aleksandra Kapedanovska Nestorovska, PhD, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Skopje, RN Macedonia, Mother Theresa str 47, 1000 Skopje, R. North Macedonia, Email address: alka@ff.ukim.edu.mk
page: 35

DISSCUSION

The main goal of optimal antiplatelet therapy for patients with acute coronary disease and/or undergoing percutaneous coronary intervention is to reduce the inci- dence of cardiovascular events. The clinical outcome of clopidogrel, as a well-established antiplatelet therapy, has high inter-individual variability within patients Although recent studies present contradictory data, our results support the association between the presence of the CYP2C19 *2, alone or in combination with the ABCB1 C and an increased risk for adverse cardiovascular events compared to the carriers of the alternative alleles. The con- comitant inheritance of the genotype CYP2C19*1/*2 and ABCB1 CT have shown a significant trend toward increased risk for MACE. These finding are line with data presented in the studies conducted on a larger sample size. (16-18). According to another study ABCB1 C3435T and CYP2C19 *2 polymorphisms are recognized as signifi- cant, independent predictors for the primary endpoint of cardiovascular death, myocardial infarction or stroke. The presented results indicate that the risk for MACE is higher in patients, either as carriers of a CYP2C19 or ABCB1 reduced-function allele, or both (19). In our study it was also demonstrated that patients with normal CYP2C19 genetic status and presence of the ABCB1 CT/CC geno- type have a higher incidence of MACE, indicating that the presence of the ABCB1 C allele could be a potential negative predictor for disease outcome in patients treated with clopidogrel. In a large cohort, conducted on 2208 patients with an acute myocardial infarction receiving clopidogrel therapy, Simon et al., presented no significant association between the ABCB1 and CYP2C19 polymorphisms and the clini- cal outcome, but the presence of two CYP2C19-deficient alleles and either one or two ABCB1 variant alleles was associated with rate of events five times higher when com- pared to patients with the wild-type (20). Another study also supports the evidence that patients who are poor me- tabolizers are at greater risk of thrombotic events when treated with clopidogrel (17, 21). Several studies including the TRITON TIMI study evaluated the contribution of ABCB1 variants in patient carrying the risk allele CYP2C19*2 and confirmed that clopidogrel response depends on the complex mecha- nisms of action, including hepatic activation and also that variable response can occur due to other factors such as polymorphisms in other genes involved in clopidogrel pharmacokinetics and pharmacodynamics. Since this study was conducted on a small sample size, limitations should be considered when interpreting the results. This was the first conducted study in Macedonia to evaluate the concomitant influence of the ABCB13435 CT and CYP2C19*1/*2 genotypes on clinical cardiovas- cular outcomes in coronary artery disease patients on clopidogrel treatment. The evaluation was based on oc- curred major adverse cardiovascular events and plasma concentrations of clopidogrel, and its active metabolites were not monitored during the follow up. Moreover, we cannot completely exclude the probability that other risk factors, such as BMI, smoking status, lifestyle, diet etc., influence the clinical cardiovascular outcome. However, the main limitation of this study was the small number of patients included, leading to restricted statistical signifi- cance for some of the results. Additional, larger studies will be of great importance to further evaluate the relation between concomitant inheritance of the ABCB1 C3435T and CYP2C19*2 polymorphisms and clopidogrel treat- ment outcomes.

Number 27 VOL. 27 (2), 2024	Number 27 VOL. 27 (1), 2024
Number 26 Number 26 VOL. 26(2), 2023 All in one	Number 26 VOL. 26(2), 2023
Number 26 VOL. 26, 2023 Supplement	Number 26 VOL. 26(1), 2023
Number 25 VOL. 25(2), 2022	Number 25 VOL. 25 (1), 2022
Number 24 VOL. 24(2), 2021	Number 24 VOL. 24(1), 2021
Number 23 VOL. 23(2), 2020	Number 22 VOL. 22(2), 2019
Number 22 VOL. 22(1), 2019	Number 22 VOL. 22, 2019 Supplement
Number 21 VOL. 21(2), 2018	Number 21 VOL. 21 (1), 2018
Number 21 VOL. 21, 2018 Supplement	Number 20 VOL. 20 (2), 2017
Number 20 VOL. 20 (1), 2017	Number 19 VOL. 19 (2), 2016
Number 19 VOL. 19 (1), 2016	Number 18 VOL. 18 (2), 2015
Number 18 VOL. 18 (1), 2015	Number 17 VOL. 17 (2), 2014
Number 17 VOL. 17 (1), 2014	Number 16 VOL. 16 (2), 2013
Number 16 VOL. 16 (1), 2013	Number 15 VOL. 15 (2), 2012
Number 15 VOL. 15, 2012 Supplement	Number 15 Vol. 15 (1), 2012
Number 14 14 - Vol. 14 (2), 2011	Number 14 The 9th Balkan Congress of Medical Genetics
Number 14 14 - Vol. 14 (1), 2011	Number 13 Vol. 13 (2), 2010
Number 13 Vol.13 (1), 2010	Number 12 Vol.12 (2), 2009
Number 12 Vol.12 (1), 2009	Number 11 Vol.11 (2),2008
Number 11 Vol.11 (1),2008	Number 10 Vol.10 (2), 2007
Number 10 10 (1),2007	Number 9 1&2, 2006
Number 9 3&4, 2006	Number 8 1&2, 2005
Number 8 3&4, 2004	Number 7 1&2, 2004
Number 6 3&4, 2003	Number 6 1&2, 2003
Number 5 3&4, 2002	Number 5 1&2, 2002
Number 4 Vol.3 (4), 2000	Number 4 Vol.2 (4), 1999
Number 4 Vol.1 (4), 1998	Number 4 3&4, 2001
Number 4 1&2, 2001	Number 3 Vol.3 (3), 2000
Number 3 Vol.2 (3), 1999	Number 3 Vol.1 (3), 1998
Number 2 Vol.3(2), 2000	Number 2 Vol.1 (2), 1998
Number 2 Vol.2 (2), 1999	Number 1 Vol.3 (1), 2000
Number 1 Vol.2 (1), 1999	Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact