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Platelet receptor Gene (P2Y12, P2Y1) and platelet glycoprotein Gene (GPIIIa) polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

Patients with minor ischemic stroke (MIS) are at high risk of recurrent ischemic stroke (RIS). The aim of this study was to evaluate the effects of platelet receptor gene (P2Y12, P2Y1) and glycoprotein gene (GPIIIa) polymorphisms, as well as their interactions, on antiplatelet drug responsiveness and clinical outcomes in patients with acute MIS.

Methods

We prospectively enrolled 426 patients with acute MIS who had been receiving combined aspirin and clopidogrel treatment for at least 3 months. Prevalence of seven variants in P2Y12, P2Y1, and GPIIIa genes were examined using mass spectrometry. Gene-gene interactions were evaluated using generalized multifactor dimensionality reduction (GMDR) analysis. Antiplatelet drug responsiveness was assessed by platelet aggregation assay. All patients were followed for 90 days. Primary outcomes were defined as a composite of RIS, myocardial infarction (MI), and death.

Results

The incidence of primary outcomes was 10.8% (46/426; 40 had RIS, 2 died, and 4 had MI) during the first 90 days after stroke. No significant differences were found regarding genotype frequencies of the seven variants between those with and without incidence of primary outcomes. However, we observed significant gene-gene interaction between rs16863323 and rs2317676 polymorphisms. The high-risk interactive genotypes were independently associated with poor antiplatelet drug responsiveness and increased risk of primary outcomes.

Conclusion

Responsiveness to antiplatelet drugs and the risks for adverse clinical events in this MIS cohort appear to be multifactorial since the outcomes were not mediated by single gene polymorphisms.

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Authors and Affiliations

  1. Department of Neurology, The People’s Hospital of Deyang City, 173 North Taishan Road, Deyang, Sichuan, 618000, China

    Xingyang Yi, Chun Wang & Ping Liu

  2. Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, 325200, China

    Qiang Zhou, Jing Lin & Cheng Fu

Authors
  1. Xingyang Yi
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  2. Qiang Zhou
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  3. Chun Wang
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  4. Jing Lin
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  5. Ping Liu
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  6. Cheng Fu
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Corresponding author

Correspondence to Chun Wang.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committees of the People’s Hospital of Deyang City and The Third Affiliated Hospital of Wenzhou Medical College and is in accordance with the principles stated in the Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Clinical Trial Registration Information: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-14004724.

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Yi, X., Zhou, Q., Wang, C. et al. Platelet receptor Gene (P2Y12, P2Y1) and platelet glycoprotein Gene (GPIIIa) polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke. Eur J Clin Pharmacol 73, 437–443 (2017). https://doi.org/10.1007/s00228-017-2198-2

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  • DOI: https://doi.org/10.1007/s00228-017-2198-2

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