Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-10-02 eCollection Date: 2023-01-01 DOI:10.2147/PGPM.S390092

Ismail Mouhrach, Laila Bouguenouch, Adil Kamal, Abbassi Meriame, Nada El Khorb, Mohammed El Azami El Idrissi, Hafid Akoudad, Hicham Bekkari

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Abstract

Introduction: Clopidogrel is an antiplatelet prodrug primarily prescribed to prevent or treat acute coronary syndrome (ACS) or acute ischemic stroke (IS), polymorphisms of genes encoding cytochrome P-450 (CYP) and P-glycoprotein transporter, could affect the efficiency of clopidogrel absorption and biotransformation, especially during the first critical hours following its administration.

Methods: The present study was designed to investigate the potential association of clopidogrel responsiveness and 14 polymorphisms in the genes encoding the CYPs (CYP2C9, 2C19, 3A4, 3A5, 1A2, and 2B6), the ATP binding cassette subfamily B member 1 (ABCB1). Platelet aggregation activity was measured after 8h of 300mg clopidogrel administration for fifty-five ACS patients.

Results: There was no significant association between polymorphism of the studied CYPs and clopidogrel responsiveness (P>0.05). The frequency of the ABCB1 3435 T allele in clopidogrel non-responders was higher (78.9%) compared to responders (52.8%), but this difference was not significant (P=0.057). Demographic characteristics, comorbidities, concomitant treatments were not associated with clopidogrel response.

Discussion: There was no effect of the studied genetic variations and demographic factors on the platelet activity of clopidogrel in Moroccan ACS patients.

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CYP450酶和ABCB1多态性对摩洛哥急性冠状动脉综合征患者氯吡格雷反应的影响。

简介：氯吡格雷是一种抗血小板前药，主要用于预防或治疗急性冠状动脉综合征（ACS）或急性缺血性中风（is），编码细胞色素P-450（CYP）和P-糖蛋白转运蛋白的基因多态性可能影响氯吡格雷的吸收和生物转化效率，尤其是在给药后的第一个关键小时。方法：本研究旨在研究氯吡格雷反应性与编码CYP（CYP2C9、2C19、3A4、3A5、1A2和2B6）、ATP结合盒亚家族B成员1（ABCB1）的14个基因多态性之间的潜在关联。55名ACS患者服用300mg氯吡格雷8小时后，测定血小板聚集活性。结果：研究的CYP多态性与氯吡格雷反应性之间没有显著相关性（P>0.05）。氯吡格雷无反应者中ABCB1 3435 T等位基因的频率（78.9%）高于有反应者（52.8%），但这一差异并不显著（P=0.057），联合治疗与氯吡格雷反应无关。讨论：研究的遗传变异和人口统计学因素对摩洛哥ACS患者氯吡格雷的血小板活性没有影响。

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来源期刊

Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

3.30

自引率

5.30%

发文量

110

审稿时长

16 weeks

期刊介绍： Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.