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CYP2C19*2/*3基因多态性患者对氯吡格雷的反应评估及其与miR-19b表达的关联。

Evaluation of response to clopidogrel in patients with CYP2C19*2/*3 polymorphisms and its association with miR-19b expression.

作者信息

Eskandarian Shiva, Zafarani Alireza, Tandel Parisa, Tamaddon Gholamhossein, Amini Ali

机构信息

Department of Hematology and Blood Banking, Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Mol Biol Rep. 2025 Apr 9;52(1):374. doi: 10.1007/s11033-025-10482-7.

Abstract

BACKGROUND

Clopidogrel is a widely used antiplatelet drug for treating acute coronary syndrome. Its metabolism primarily involves the CYP2C19 isoenzyme, with CYP2C192 and CYP2C193 alleles associated with reduced metabolic activity. MicroRNAs, particularly miR-19b, have been linked to cardiovascular disease, but their role in clopidogrel metabolism remains unclear.

METHODS

A cross-sectional study was conducted on 50 middle-aged patients on clopidogrel therapy. Platelet aggregation was measured using adenosine diphosphate-induced assays, while CYP2C19*2/*3 polymorphisms were analyzed via RFLP-PCR. The expression of miR-19b was assessed using Real Time-PCR. Statistical analyses were performed to evaluate the relationship between genetic variations, platelet aggregation, and miR-19b expression.

RESULTS

The study revealed that 68% of the patients had wild-type genotypes, while 26% had CYP2C19*1/3, 4% had CYP2C193/3, and 2% had CYP2C191/2 genotypes. Patients with CYP2C191/3 polymorphisms exhibited significantly higher mean platelet aggregation compared to those with wild-type genotypes, suggesting a reduced response to clopidogrel treatment. Additionally, the expression of miR-19b did not show significant variation across the different genotypes, indicating that miR-19b may not play a substantial role in clopidogrel metabolism.

CONCLUSION

Patients with CYP2C19*1/*3 polymorphisms have a reduced response to clopidogrel, emphasizing the importance of genetic testing to personalize antiplatelet therapy. The lack of association between miR-19b expression and clopidogrel metabolism suggests that miR-19b is not a critical factor in treatment response.

摘要

背景

氯吡格雷是一种广泛用于治疗急性冠状动脉综合征的抗血小板药物。其代谢主要涉及细胞色素P450 2C19(CYP2C19)同工酶,CYP2C192和CYP2C193等位基因与代谢活性降低有关。微小RNA,尤其是miR-19b,已被证明与心血管疾病有关,但其在氯吡格雷代谢中的作用仍不清楚。

方法

对50例接受氯吡格雷治疗的中年患者进行了一项横断面研究。采用二磷酸腺苷诱导试验测量血小板聚集,通过限制性片段长度多态性聚合酶链反应(RFLP-PCR)分析CYP2C19*2/*3基因多态性。使用实时聚合酶链反应评估miR-19b的表达。进行统计分析以评估基因变异、血小板聚集和miR-19b表达之间的关系。

结果

研究发现,68%的患者具有野生型基因型,而26%的患者具有CYP2C19*1/3基因型,4%的患者具有CYP2C193/3基因型,2%的患者具有CYP2C191/2基因型。与野生型基因型患者相比,具有CYP2C191/3基因多态性的患者平均血小板聚集显著更高,这表明对氯吡格雷治疗的反应降低。此外,miR-19b的表达在不同基因型之间没有显著差异,这表明miR-19b可能在氯吡格雷代谢中不起重要作用。

结论

具有CYP2C19*1/*3基因多态性的患者对氯吡格雷的反应降低,这强调了基因检测对个性化抗血小板治疗的重要性。miR-19b表达与氯吡格雷代谢之间缺乏关联表明,miR-19b不是治疗反应的关键因素。

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