Abstract：
Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy. This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants. No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process.
摘要：
抗血小板治疗,急性冠状动脉综合征（ACS）患者经皮冠状动脉介入治疗（PCI）的护理金标准，是与药物不良反应（ADR）发展最相关的治疗方法之一。尽管许多研究表明，基于有限数量的高证据变体（主要是CYP2C19*2和*3）的药物干预可以降低主要不良心血管事件（MACE）的发生率。尽管进行了个性化治疗，但ADR的发生率仍然不同（在我们的病例中为10.1％）。这项研究旨在通过设计和分析靶向基因组来鉴定PCI后12个月与MACEs终点相关的新遗传变异。我们对244例ACS-PCI支架患者（109例有事件，135例无事件）和99例无结构性心血管疾病的对照进行了测序，并进行了关联分析以寻找意外的遗传变异。校正后没有单核苷酸多态性达到基因组意义，但是三个新颖的变体，包括ABCA1（rs2472434），KLB(rs17618244),和ZNF335（rs3827066），可能在ACS患者的MACE中发挥作用。这些遗传变异参与调节高密度脂蛋白水平和胆固醇沉积,因为它们是监管变体，它们可能影响附近脂质代谢相关基因的表达。我们的研究结果表明，新的靶标（在基因和途径水平）可能会增加对MACEs的易感性，但在将这些发现纳入治疗决策过程之前,还需要进一步的研究来阐明所鉴定的变异的作用和影响.
