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体重、CYP2C19 和 P2Y12 受体多态性与阿司匹林不耐受的中国缺血性脑卒中患者氯吡格雷抵抗相关。

Body weight, CYP2C19, and P2Y12 receptor polymorphisms relate to clopidogrel resistance in a cohort of Chinese ischemic stroke patients with aspirin intolerance.

机构信息

Department of Neurology, The First People's Hospital of Shangqiu City Affiliated to Xinxiang Medical University, Shangqiu, China.

Department of Neurology, The First People's Hospital of Shangqiu City Affiliated to Xuzhou Medical University, Shangqiu, China.

出版信息

Eur J Clin Pharmacol. 2020 Nov;76(11):1517-1527. doi: 10.1007/s00228-020-02946-5. Epub 2020 Jul 6.

DOI:10.1007/s00228-020-02946-5
PMID:32632713
Abstract

PURPOSE

Dual antiplatelet therapy (DAT) with clopidogrel and aspirin is not suitable for clopidogrel resistance (CR) patients with aspirin intolerance. To investigate the prevalence of CR in patients with aspirin intolerance after ischemic stroke (IS) and to assess the relationship between CR and CYP2C19, P2Y12 receptor genotypes in patients with aspirin intolerance after IS.

METHODS

We enrolled 126 IS patients with aspirin intolerance from Han Chinese in Shangqiu from January 2016 to November 2018. All IS patients with aspirin intolerance were treated with clopidogrel for 7 days. Adenosine diphosphate-induced platelet inhibition rate was measured by thrombelastography (TEG) mapping assay. The SNPs CYP2C192, CYP2C193, and P2Y12 receptor (52 G >T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Binary logistic regression analyses were performed using SPSS version 20.0.

RESULTS

The prevalence of CR in patients with aspirin intolerance after IS was approximately 31.0%. Multivariate regression analysis showed that body weight (OR 1.091 (95% CI 1.031-1.155), p = 0.003), CYP2C19 phenotype intermediate metabolizer (IM) (OR 3.820 (95% CI 1.021-14.288), p = 0.046), and CYP2C19 phenotype poor metabolizer (PM) (OR 14.481 (95% CI 2.791-75.129), p = 0.001) significantly increased the risk of CR and P2Y12 receptors (52 G >T) (OR 3.498 [95% CI 1.251-9.784], p = 0.017) increased the risk of CR.

CONCLUSIONS

The patients with high body weight, the CYP2C19 phenotypes, and P2Y12 receptor (52 G >T) variant alleles are at risk of CR during clopidogrel treatment in Chinese IS patients with aspirin intolerance. The higher body weight and relevant polymorphisms may help to predict CR in Chinese IS patients with aspirin intolerance.

摘要

目的

氯吡格雷和阿司匹林的双联抗血小板治疗(DAT)不适合对阿司匹林不耐受的氯吡格雷抵抗(CR)患者。本研究旨在调查缺血性脑卒中(IS)后对阿司匹林不耐受患者中 CR 的流行情况,并评估 CR 与 CYP2C19、P2Y12 受体基因型在 IS 后对阿司匹林不耐受患者中的关系。

方法

本研究纳入了 2016 年 1 月至 2018 年 11 月来自河南商丘的 126 例 IS 后对阿司匹林不耐受的汉族患者。所有 IS 后对阿司匹林不耐受的患者均接受氯吡格雷治疗 7 天。采用血栓弹力图(TEG)图谱法测定二磷酸腺苷诱导的血小板抑制率。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对 CYP2C192、CYP2C193 和 P2Y12 受体(52 G > T)的 SNP 进行基因分型。采用 SPSS 20.0 版进行二元逻辑回归分析。

结果

IS 后对阿司匹林不耐受患者中 CR 的患病率约为 31.0%。多变量回归分析显示,体重(OR 1.091(95%CI 1.031-1.155),p = 0.003)、CYP2C19 表型中间代谢者(IM)(OR 3.820(95%CI 1.021-14.288),p = 0.046)和 CYP2C19 表型弱代谢者(PM)(OR 14.481(95%CI 2.791-75.129),p = 0.001)显著增加 CR 的风险,而 P2Y12 受体(52 G > T)(OR 3.498(95%CI 1.251-9.784),p = 0.017)则增加了 CR 的风险。

结论

在接受氯吡格雷治疗的中国 IS 后对阿司匹林不耐受的患者中,体重较高、CYP2C19 表型和 P2Y12 受体(52 G > T)变异等位基因的患者发生 CR 的风险较高。较高的体重和相关多态性可能有助于预测中国 IS 后对阿司匹林不耐受患者的 CR。

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