Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Beijing, China.
Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Clin Ther. 2024 Aug;46(8):644-649. doi: 10.1016/j.clinthera.2024.06.019. Epub 2024 Jul 26.
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.
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.
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).
The polygenetic model may be useful for clopidogrel drug response prediction in patients with CAD.
患有冠状动脉疾病 (CAD) 的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。药物基因组学研究表明，药物反应也可能受到遗传变异的影响，并且多个遗传变异可能共同起作用。我们假设携带更多风险等位基因的患者可能对氯吡格雷的药物反应更差，并且整合不同单变体的多基因模型可能有潜力更好地解释氯吡格雷药物反应的可变性。我们旨在研究多基因模型是否可用于预测氯吡格雷的药物反应。
共有 935 名 CAD 患者入组研究。我们研究了 19 个与氯吡格雷相关的单核苷酸多态性 (SNP) 与复发性缺血事件发生之间的关联。此外，构建了多基因模型来评估缺血事件的风险。
只有 CYP2C8 基因的 2 个 SNP（rs1934980 和 rs17110453）与复发性缺血事件的发生具有名义上的关联。我们构建了一个整合 6 个与氯吡格雷相关的 SNP 的多基因模型。与携带 6 个或更少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 CAD 患者对氯吡格雷的药物反应。
