Body weight, CYP2C19 , and P2Y12 receptor polymorphisms relate to clopidogrel resistance in a cohort of Chinese ischemic
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PHARMACOGENETICS
Body weight, CYP2C19, and P2Y12 receptor polymorphisms relate to clopidogrel resistance in a cohort of Chinese ischemic stroke patients with aspirin intolerance Zhiqiang Li 1,2 & Wanqing Dong 1 & Daorong Yang 3 & Linhai Sun 1 & Xianjun He 1 & Huanhuan Hu 4 & Jianping Zhang 1 & Chunyu Wang 1 & Yulin Li 5 & Ming Zhao 1 & Yu Kong 1 & Yan Wang 1 Received: 28 December 2019 / Accepted: 23 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 CYP2C19*2, CYP2C19*3, 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. Keywords Ischemic stroke . Antithrombotic therapy . Clopidogrel resistance . Polymorphisms . Aspirin intolerance
* Zhiqiang Li [email protected] Wanqing Dong [email protected] Daorong Yang [email protected] Linhai Sun [email protected] Xianjun He [email protected] Huanhuan Hu [email protected]
Jianping Zhang [email protected] Chunyu Wang [email protected] Yulin Li [email protected] Ming Zhao [email protected] Yu Kong [email protected] Yan Wang [email protected] Extended author information available on the last page of the article
Eur J Clin Pharmacol
Introduction
Methods
The cerebrovascular disease has now become the major reason for death in China, and the related burden has been expected to increase over the comi
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