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Anal Chem. 2023 Jul 4;95(26):10127-10135. doi: 10.1021/acs.analchem.3c01968. Epub 2023 Jun 16.
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Safety and Efficacy of Selective, Clopidogrel-Based Strategies in Acute Coronary Syndrome: A Study-Level Meta-analysis.急性冠状动脉综合征中基于选择性、氯吡格雷的治疗策略的安全性和疗效:一项研究水平的荟萃分析。
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PEAR1、PON1、CYP2C19、CYP1A2和F2R基因多态性与接受经皮冠状动脉介入治疗的急性冠状动脉综合征患者使用氯吡格雷治疗时发生主要不良心血管事件相关。

PEAR1, PON1, CYP2C19, CYP1A2 and F2R Polymorphisms are Associated with MACE in Clopidogrel-Treated Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

作者信息

Du Pengqiang, Li Xingang, Li Dandan, Ma Yongcheng, Ni Ming, Li Yafei, Li Wenbo, Wang Aifeng, Xu Xiaowei

机构信息

Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Henan Provincial People's Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, 450003, People's Republic of China.

Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2024 Dec 21;17:611-621. doi: 10.2147/PGPM.S490030. eCollection 2024.

DOI:10.2147/PGPM.S490030
PMID:39723111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11669274/
Abstract

OBJECTIVE

The objective of this study was to evaluate the impact of clopidogrel-related gene polymorphisms on the occurrence of recurrent thrombotic events and cardiovascular death in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI).

METHODS

We conducted genotype testing for 26 specific loci mapped to 18 clopidogrel-associated genes in ACS patients who had undergone PCI and were receiving dual antiplatelet therapy only involving clopidogrel. We documented major adverse cardiovascular events (MACE) and clinical endpoints, analyzing the effect of genetic polymorphisms on treatment outcomes.

RESULTS

A total of 200 patients were enrolled in the study, with ischemic events occurring in 21 cases. Carriers of the T-allele for rs41273215 (), rs662 (), and the A-allele for rs4244285 (), as well as the C-allele for rs762551 (), exhibited a significant increase in the risk of MACE (OR = 2.76, 95% CI = 1.46-5.22, P = 0.002; OR = 3.72, 95% CI = 1.82-7.64, P = 0.0003; OR = 3.86, 95% CI = 1.89-7.86, P = 0.0002; OR = 2.40, 95% CI = 1.27-4.55, P = 0.007). Notably, the variant T-allele of rs168753 () was associated with a significant reduction in the risk of such events (OR = 0.29, 95% CI = 0.12-0.67, P = 0.004). No significant associations were found between other single nucleotide polymorphisms (SNPs) and clinical endpoints.

CONCLUSION

Polymorphisms in rs41273215 (), rs662 (), rs4244285 (), and rs762551 () were correlated with an increased risk of MACE in PCI patients. Conversely, the rs168753 () polymorphism was linked to improved cardiovascular outcomes. Genotyping for these polymorphisms could be instrumental in identifying patients at heightened risk for MACE.

摘要

目的

本研究旨在评估氯吡格雷相关基因多态性对接受经皮冠状动脉介入治疗(PCI)的急性冠状动脉综合征(ACS)患者复发性血栓事件发生及心血管死亡的影响。

方法

我们对接受PCI且仅接受氯吡格雷双联抗血小板治疗的ACS患者中映射到18个氯吡格雷相关基因的26个特定基因座进行了基因分型检测。我们记录了主要不良心血管事件(MACE)和临床终点,分析基因多态性对治疗结果的影响。

结果

本研究共纳入200例患者,其中21例发生缺血事件。rs41273215()的T等位基因携带者、rs662()的T等位基因携带者、rs4244285()的A等位基因携带者以及rs762551()的C等位基因携带者发生MACE的风险显著增加(OR = 2.76,95%CI = 1.46 - 5.22,P = 0.002;OR = 3.72,95%CI = 1.82 - 7.64,P = 0.0003;OR = 3.86,95%CI = 1.89 - 7.86,P = 0.0002;OR = 2.40,95%CI = 1.27 - 4.55,P = 0.007)。值得注意的是,rs168753()的变异T等位基因与此类事件风险的显著降低相关(OR = 0.29,95%CI = 0.12 - 0.67,P = 0.004)。未发现其他单核苷酸多态性(SNP)与临床终点之间存在显著关联。

结论

rs41273215()、rs662()、rs4244285()和rs762551()的多态性与PCI患者发生MACE的风险增加相关。相反,rs168753()多态性与改善的心血管结局相关。对这些多态性进行基因分型有助于识别发生MACE风险较高的患者。