CYP2C19基因变异对阿拉伯经皮冠状动脉介入治疗及支架植入术患者出血及主要心血管不良事件的影响

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Zainab Omer Ali, Loulia Bader, Shaaban Mohammed, Salaheddin Arafa, Abdulrahman Arabi, Larisa Cavallari, Taimour Langaee, Fatima Mraiche, Nasser Rizk, Ahmed Awaisu, Mohamed H Shahin, Hazem Elewa
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引用次数: 4

摘要

三分之一的患者有氯吡格雷耐药,可能导致严重心脏不良事件(mace)。相比之下,发现一些氯吡格雷治疗的患者有高反应性血小板,这与较高的出血风险有关。一些研究表明,编码CYP2C19基因的多态性有助于对氯吡格雷反应的变异性。影响阿拉伯人群氯吡格雷反应的遗传和非遗传因素的数据很少。在这项前瞻性队列研究中,我们试图评估功能等位基因(CYP2C19*17)增加与出血事件之间的关系,并验证CYP2C19遗传变异和非遗传因素对mace发生率的影响。方法:在卡塔尔多哈一家专科三级医院心脏医院接受经皮冠状动脉介入治疗并接受氯吡格雷治疗的患者采集血液样本。随访12个月。采用TaqMan法对CYP2C19*2、*3和*17进行基因分型。结果:254例患者中*2、*3、*17的次要等位基因频率分别为0.13、0.004、0.21。在12个月的随访期间,有21例出血事件(8.5例/100例患者年)。CYP2C19*17携带者与出血风险增加相关(OR, 21.6;95% ci, 4.8-96.8;P < 0.0001)。发现CYP2C19*2或*3携带者与基线和事件MACE合并风险增加相关(or, 8.4;95% ci, 3.2-23.9;P < 0.0001)。结论:本研究显示CYP2C19*17等位基因与出血风险增加有显著相关性,CYP2C19*2或*3与MACE结局有显著相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of CYP2C19 genetic variants on bleeding and major adverse cardiovascular events in a cohort of Arab patients undergoing percutaneous coronary intervention and stent implantation.

Introduction: One-third of patients have clopidogrel resistance that may lead to major adverse cardiac events (MACEs). By contrast, it was found that some clopidogrel-treated patients have hyperresponsive platelets that are associated with higher bleeding risk. Several studies have shown that polymorphisms in the gene encoding the CYP2C19 contribute to the variability in response to clopidogrel. Data on genetic and nongenetic factors affecting clopidogrel response in the Arab population are scarce. In this prospective cohort study, we sought to assess the association between the increased function allele (CYP2C19*17) and bleeding events, and validate the effect of the CYP2C19 genetic variants and nongenetic factors on the incidence of MACEs.

Methods: Blood samples were collected from patients that were undergoing percutaneous coronary intervention and receiving clopidogrel at the Heart Hospital, a specialist tertiary hospital in Doha, Qatar. Patients were followed for 12 months. Genotyping was performed for CYP2C19*2, *3, and *17 using TaqMan assays.

Results: In 254 patients, the minor allele frequencies were 0.13, 0.004, and 0.21 for *2, *3, and *17, respectively. Over a 12-month follow-up period, there were 21 bleeding events (8.5 events/100 patient-year). CYP2C19*17 carriers were found to be associated with increased risk of bleeding (OR, 21.6; 95% CI, 4.8-96.8; P < 0.0001). CYP2C19*2 or *3 carriers were found to be associated with increased risk of baseline and incident MACE combined (OR, 8.4; 95% CI, 3.2-23.9; P < 0.0001).

Conclusion: This study showed a significant association between CYP2C19*17 allele and the increased risk of bleeding, and CYP2C19*2 or *3 with MACE outcomes.

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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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