Zhongguo cuzhong zazhi (Oct 2024)
基于药物基因组学的急性缺血性卒中个体化抗栓治疗进展 Advances in Pharmacogenomics-Based Individualized Antithrombotic Therapy for Acute Ischemic Stroke
Abstract
抗栓治疗是预防急性缺血性卒中复发的关键手段。随着多组学研究的进展和越来越多影响药物安全性和有效性的相关基因被发现，药物基因组学在个体化治疗中的应用逐渐受到关注。本文阐述了药物基因组学在急性缺血性卒中患者抗栓治疗中的指导作用的研究进展，旨在挖掘通过基因检测优化药物选择与剂量调整的潜力。研究表明，氯吡格雷等药物的疗效因细胞色素P450酶家族2亚家族C成员19（cytochrome P450 family 2 subfamily C member 19，CYP2C19）基因多态性而异，携带CYP2C19*2或CYP2C19*3等功能缺失等位基因的患者对标准抗血小板治疗反应较差，不能有效降低卒中复发风险，但通过基因检测指导药物选择可以显著提高治疗效果。此外，心源性卒中患者目前常选择华法林或新型口服抗凝药作为主要的抗栓治疗选择。华法林的剂量效应与多个基因，如细胞色素P450酶家族2亚家族C成员9（cytochrome P450 family 2 subfamily C member 9，CYP2C9）和维生素K环氧化物还原酶C1（vitamin K epoxide reductase complex 1，VKORC1）的多态性密切相关。基因检测能够帮助医师个体化调整华法林剂量，减少出血或血栓事件的发生。综上所述，药物基因组学在急性缺血性卒中抗栓治疗中的应用为个体化治疗提供了新的思路，未来有望进一步提高治疗的安全性和有效性。 Abstract: Antithrombotic therapy is a key measure for preventing acute ischemic stroke recurrence. With the advancement of multi-omics research and the identification of more genes affecting drug safety and efficacy, pharmacogenomics is gaining attention for its role in individualized therapy. This paper reviews the progress of research on pharmacogenomics in guiding antithrombotic therapy for patients with acute ischemic stroke, aiming to elucidate the potential of gene detection in optimizing drug selection and dosage adjustments. Studies have shown that the efficacy of drugs like clopidogrel is modulated by polymorphisms in the cytochrome P450 family 2 subfamily C member 19 (CYP2C19) gene. Patients carrying loss-of-function alleles such as CYP2C19*2 or CYP2C19*3 demonstrate diminished responses to standard antiplatelet therapy and cannot effectively reduce the risk of stroke recurrence. However, gene detection can significantly improve treatment outcomes by guiding drug selection. Additionally, for patients with cardioembolic stroke, warfarin or novel oral anticoagulants are commonly used as primary antithrombotic treatment options. The dosage effects of warfarin are closely related to the polymorphisms in genes such as cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1). Gene detection can help physicians individualize warfarin dosing, reducing the occurrence of bleeding or thrombotic events. In conclusion, the application of pharmacogenomics in antithrombotic therapy for acute ischemic stroke provides a new idea for individualized therapy, with the potential to further improve the safety and efficacy in the future.
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