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Should CYP2C19 Genotyping Be Recommended as a Straight Forward Approach to Optimize Clopidogrel Utilization in Patients with Ischemic Stroke Complicated by Type 2 Diabetes Mellitus?

Authors Sun J, Leng P, Sun C, Xu W, Zhao Z, Li X, Zhang X, Li J

Received 8 September 2020

Accepted for publication 30 October 2020

Published 23 November 2020 Volume 2020:13 Pages 645—653

DOI https://doi.org/10.2147/PGPM.S279719

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth


Jialin Sun,1,* Ping Leng,1 Chen Sun,2 Wen Xu,1 Zhenhuan Zhao,1 Xiao Li,1 Xiaolei Zhang,1 Jing Li1,*

1Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, People’s Republic of China; 2Department of Pharmacy, Qingdao Municipal Hospital, Qingdao 266003, Shandong, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jialin Sun; Jing Li
Department of Pharmacy, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao 266003, Shandong, People’s Republic of China
Tel +86-532-82912261; +86-532-82911566
Email sjlsyyk-412@163.com; stella_71@tom.com

Background: There have been few studies on CYP2C19 genotypes and clopidogrel response associated with ischemic stroke (IS), especially IS complicated by type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association between CYP2C19 polymorphisms and high on-treatment platelet reactivity (HTPR) in IS patients with T2DM in China.
Patients and Methods: A total of 426 consecutive IS patients with T2DM were enrolled in this case-control study and they were divided into HTPR group and non-HTPR group according to the ADP-induced platelet inhibition (PIADP) assessed by thromboelastography (TEG). Genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Various clinical and demographic data were also recorded. The association between CYP2C19 genetic variants and platelet function was assessed.
Results: Carriers of CYP2C19*2 heterozygous and mutant homozygous genotypes showed significantly lower PIADP than non-carriers (27.2% vs 38.3%, p < 0.001; 27.41% vs 38.3%, p = 0.012, respectively). Compared with the control group, the CYP2C19*2 A allele was more frequent in the HTPR group (34.51% vs 25.82%, p = 0.002). The carriage of CYP2C19*2 mutant allele was significantly associated with increased risk of HTPR (odds ratio (OR) = 1.94, 95% confidence interval (CI) = 1.32– 2.85). There was no significant correlation between CYP2C19*3 or *17 genotypes and HTPR risk.
Conclusion: CYP2C19*2 mutant allele was associated with attenuated platelet response to clopidogrel and increased risk of HTPR in IS patients with T2DM, suggesting that CYP2C19*2 polymorphism might be an important predictor of HTPR in this high-risk population.

Keywords: clopidogrel, ischemic stroke, type 2 diabetes mellitus, CYP2C19, high on-treatment platelet reactivity

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