Pharmacogenomic Polygenic Model of Clopidogrel Predicts Recurrent Ischemic Events in Chinese Patients With Coronary Artery Disease

IF 3.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical therapeutics Pub Date : 2024-08-01 DOI:10.1016/j.clinthera.2024.06.019

Xinyi Zhang MSc , Yuchun Cai MSc , Pei Zhou MD , Wenchang Nie MM , Haoning Sun MD , Yutong Sun MD , Yuxuan Zhao MSc , Congxiao Han MSc , Chengfu Cao MD , Jian Liu MD , Xiaoyan Nie PhD

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引用次数: 0

Abstract

Purpose

Patients with coronary artery disease (CAD) need to take antiplatelet drugs regularly in order to prevent thrombosis; however, there is existing inter-individual variability in drug response. Pharmacogenomic studies indicate that drug response may also be influenced by genetic variants, and multiple genetic variants may work together. We assumed that patients carrying more risk alleles might have a worse clopidogrel drug response and that a polygenic model integrated different single variants might have the potential to explain clopidogrel drug response variability better. We aimed to investigate whether the polygenic model could be used to predict clopidogrel drug response.

Methods

A total of 935 CAD patients were enrolled in the study. We investigated the association between 19 clopidogrel-related single-nucleotide polymorphisms (SNPs) and the incidence of recurrent ischemic events. Additionally, a polygenic model was constructed to assess the risk of ischemic events.

Findings

There were only 2 SNPs of CYP2C8 gene (rs1934980 and rs17110453) that were nominally associated with incidence of recurrent ischemic events. We constructed a polygenic model integrated with 6 clopidogrel-related SNPs. When compared with patients carrying 6 or fewer risk alleles, patients with 7 or more risk alleles had a higher risk of ischemic events (hazard ratio = 1.87; P = 0.04).

Implications

The polygenetic model may be useful for clopidogrel drug response prediction in patients with CAD.

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氯吡格雷的药物基因组多基因模型可预测中国冠心病患者的复发性缺血事件

目的：冠状动脉疾病（CAD）患者需要定期服用抗血小板药物以预防血栓形成；然而，药物反应存在个体间差异。药物基因组研究表明，药物反应也可能受到基因变异的影响，而且多种基因变异可能共同作用。我们假定，携带更多风险等位基因的患者对氯吡格雷的药物反应可能更差，而整合了不同单一变异体的多基因模型有可能更好地解释氯吡格雷药物反应的变异性。我们旨在研究多基因模型是否可用于预测氯吡格雷药物反应：研究共招募了 935 名 CAD 患者。我们研究了 19 个氯吡格雷相关单核苷酸多态性（SNPs）与复发性缺血事件发生率之间的关联。此外，我们还构建了一个多基因模型来评估缺血事件的风险：结果：CYP2C8基因中仅有2个SNPs（rs1934980和rs17110453）与复发性缺血事件的发生率存在名义上的相关性。我们构建了一个整合了 6 个氯吡格雷相关 SNP 的多基因模型。与携带 6 个或更少的风险等位基因的患者相比，携带 7 个或更多风险等位基因的患者发生缺血事件的风险更高（危险比 = 1.87；P = 0.04）：多基因模型可能有助于预测冠心病患者对氯吡格雷药物的反应。

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

Clinical therapeutics 医学-药学

CiteScore

6.00

自引率

3.10%

发文量

154

审稿时长

9 weeks

期刊介绍： Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.