Impact of ABCB1 gene polymorphism on clopidogrel plasma concentration and cardiovascular events in post-PCI patients.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics Pub Date : 2025-07-21 DOI:10.1080/14622416.2025.2534325

Abdur Razaq, Waheed Iqbal, Syed Tahir Shah, Muhammad Abdur Rauf, Nasser M Aldekhail, Filip Van Nieuwerburgh, Sami Siraj

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引用次数: 0

Abstract

Aim: This study investigated the impact of ABCB1 gene polymorphisms on clopidogrel absorption and therapeutic response by analyzing plasma levels of the clopidogrel carboxylic acid metabolite (CAM), and cardiovascular events (CVEs) in patients undergoing percutaneous coronary intervention (PCI).

Methods: A prospective cohort study of 264 post-PCI patients was conducted in Peshawar, Pakistan. CVEs over 12 months were recorded. Plasma concentrations of CAM were measured by high-performance liquid chromatography (HPLC), while the ABCB1 gene (rs1045642) was genotyped by Sanger sequencing to determine associations between genetic variants, CAM levels, and clinical outcomes.

Results: The study documented 54 CVEs, including 13 deaths, 6 stent thromboses, 10 recurrent myocardial infarctions, 23 ischemic events requiring hospitalization, and 2 strokes. The analysis showed that 31.1% of patients had subtherapeutic CAM levels ( <2000 ng/ml), while 68.9% had therapeutic levels. Genetic analysis identified 65% as poor absorbers (CT/TT genotypes) and 35% as good absorbers (CC genotype), while CAM levels were significantly associated with the CT/TT genotype (p < 0.005).

Conclusion: This study linking ABCB1 variation to CAM concentration and therapeutic outcomes. There was a significant association between ABCB1 variants and CAM concentrations. However, no association was found between ABCB1 polymorphisms and CVEs.

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ABCB1基因多态性对pci术后患者氯吡格雷血药浓度及心血管事件的影响

目的：本研究通过分析经皮冠状动脉介入治疗（PCI）患者血浆氯吡格雷羧酸代谢物（CAM）水平和心血管事件（CVEs），探讨ABCB1基因多态性对氯吡格雷吸收和治疗反应的影响。方法：在巴基斯坦白沙瓦对264例pci术后患者进行前瞻性队列研究。记录12个月以上的cve。采用高效液相色谱法（HPLC）测定血浆中CAM浓度，同时通过Sanger测序对ABCB1基因（rs1045642）进行基因分型，以确定基因变异、CAM水平和临床结果之间的关系。结果：该研究记录了54例cve，包括13例死亡、6例支架血栓形成、10例复发性心肌梗死、23例需要住院治疗的缺血性事件和2例中风。分析显示31.1%的患者有亚治疗CAM水平(p)。结论：本研究将ABCB1变异与CAM浓度和治疗结果联系起来。ABCB1变异与CAM浓度之间存在显著关联。然而，ABCB1多态性与cve之间没有关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.