Association of FMO3 rs1736557 polymorphism with clopidogrel response in Chinese patients with coronary artery disease
Association of FMO3 rs1736557 polymorphism with clopidogrel response in Chinese patients with coronary artery disease
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FMO3 rs1736557 多态性与中国冠心病患者氯吡格雷反应的关系
DOI：
10.1007/s00228-020-03024-6
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Chen XP
中科院分区：
文献类型：
--
作者：
Zhu KX;Song PY;He-Li;Li MP;Du YX;Ma QL;Peng LM;Chen XP
目的：阿司匹林和氯吡格雷双重抗血小板治疗常用于冠心病（CAD）患者经皮冠状动脉介入治疗，以预防支架内血栓形成和缺血事件。然而，一些患者在氯吡格雷治疗期间表现出高的治疗期血小板反应性（HTPR）。遗传因素如CYP2C19的功能丧失变异被证实可增加HTPR的风险。据报道，含黄素单加氧酶3 （FMO3）与血小板反应性和血栓形成的效力有关。本研究旨在探讨FMO3 rs1736557多态性与氯吡格雷反应的关系。方法：在湘雅医院接受双重抗血小板治疗的冠心病患者522例。口服300 mg负荷剂量（LD）氯吡格雷12-24小时或75 mg每日维持剂量（MD）氯吡格雷至少5天后，通过血管扩张剂刺激磷酸化试验测定血小板反应指数（PRI）。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对FMO3 rs1736557、CYP2C19*2和CYP2C19*3多态性进行基因分型。结果：CYP2C19代谢不良者（PMs）和中间代谢者（IMs）的平均PRI值显著高于广泛代谢者（EMs） （p < 0.001）。此外，FMO3 rs1736557 AA纯合子在整个队列和MD队列中与主要rs1736557 G等位基因携带者相比，PRI显著降低（p = 0.011, p = 0.008）。rs1736557 A等位基因携带者HTPR发生风险显著降低(AA vs GG: OR = 0.316, 95% CI: 0.137 ~ 0.726, p = 0.005; AA vs GA: OR = 0.249, 95% CI: 0.104 ~ 0.597, p = 0.001；AA vs GG+GA: OR = 0.294, 95% CI: 0.129 ~ 0.669, p = 0.002)，且主要存在于携带CYP2C19 LOF等位基因的患者和服用md的患者中。结论：FMO3 rs1736557 AA基因型与中国冠心病患者氯吡格雷抗血小板效价升高有关。需要进一步的研究来证实这一发现。
Purpose:Dual antiplatelet therapy with aspirin and clopidogrel is commonly used for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention to prevent stent thrombosis and ischemic events. However, some patients show high on-treatment platelet reactivity (HTPR) during clopidogrel therapy. Genetic factors such as loss-of-function variants of CYP2C19 are validated to increase the risk of HTPR. Flavin-containing monooxygenase 3 (FMO3) is reported to be associated with potency of platelet responsiveness and thrombosis. This study aimed to explore the association between FMO3 rs1736557 polymorphism and clopidogrel response.Methods:Five hundred twenty-two Chinese CAD patients treated with dual antiplatelet therapy were recruited from Xiangya Hospital. After oral administration of 300 mg loading dose (LD) clopidogrel for 12-24 h or 75 mg daily maintenance dose (MD) clopidogrel for at least 5 days, the platelet reaction index (PRI) was determined by vasodilator-stimulated phosphoprotein-phosphorylation assay. FMO3 rs1736557, CYP2C19*2, and CYP2C19*3 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results:Mean PRI value was significantly higher in CYP2C19 poor metabolizers (PMs) and intermediate metabolizers (IMs) than the extensive metabolizers (EMs) (p < 0.001). In addition, FMO3 rs1736557 AA homozygotes showed significantly lower PRI as compared with carriers of the major rs1736557 G allele in the entire cohort and in the MD cohort (p = 0.011, p = 0.008, respectively). The risk of HTPR was decreased significantly in carriers of the rs1736557 A allele (AA vs GG: OR = 0.316, 95% CI: 0.137-0.726, p = 0.005; AA vs GA: OR = 0.249, 95% CI: 0.104-0.597, p = 0.001; AA vs GG+GA: OR = 0.294, 95% CI: 0.129-0.669, p = 0.002), and the association was observed mainly in patients carrying the CYP2C19 LOF allele and in those administered with MD.Conclusion:The FMO3 rs1736557 AA genotype was related to an increased the antiplatelet potency of clopidogrel in Chinese CAD patients. Additional studies are required to verify this finding.
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影响因子：
2.1
作者：
Amin AM;Sheau Chin L;Azri Mohamed Noor D;Sk Abdul Kader MA;Kah Hay Y;Ibrahim B
通讯作者：
Ibrahim B
DOI：
10.1111/j.1440-1681.2008.04915.x
发表时间：
2008-08-01
影响因子：
2.9
作者：
Chen, Bi-Lian;Zhang, Wei;Zhou, Hong-Hao
通讯作者：
Zhou, Hong-Hao
影响因子：
7.5
作者：
A. Tsantes;I. Ikonomidis;I. Papadakis;S. Bonovas;A. Gialeraki;C. Kottaridi;E. Kyriakou;S. Kokori;P. Douramani;P. Kopterides;P. Karakitsos;J. Lekakis;V. Kapsimali
通讯作者：
A. Tsantes;I. Ikonomidis;I. Papadakis;S. Bonovas;A. Gialeraki;C. Kottaridi;E. Kyriakou;S. Kokori;P. Douramani;P. Kopterides;P. Karakitsos;J. Lekakis;V. Kapsimali
影响因子：
5.6
作者：
Canyelles M;Tondo M;Cedó L;Farràs M;Escolà-Gil JC;Blanco-Vaca F
通讯作者：
Blanco-Vaca F
DOI：
10.1111/1440-1681.12325
发表时间：
2015-01
影响因子：
2.9
作者：
Yinzhuang Zhang;Bi-Lian Chen;Wei Zhang;Xing-zhi Cao
通讯作者：
Yinzhuang Zhang;Bi-Lian Chen;Wei Zhang;Xing-zhi Cao