Association between CYP2C9 polymorphisms and ischemic stroke following endovascular neurointervention

Subhashaan Sreedharan, Leonid Churilov, Jianxiong Chan, Marian Todaro, Alan Coulthard, Jeffrey Hocking, Kate Mahady, Peter Mitchell, Richard Dowling, Steven Bush, Patrick Kwan, Bernard Yan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: Polymorphisms in the CYP2C9 gene may be associated with adverse vascular events following endovascular procedures independent of antiplatelet therapy. We aimed to investigate the impact of CYP2C9 loss-of-function polymorphisms on adverse vascular events following neurointervention. Patients and Methods: Consecutive patients undergoing neurointervention were prospectively recruited between 2010 and 2016. Patients were genotyped for the CYP2C9*2 and *3 loss-of-function polymorphisms. On the basis of possible genetic influence on antiplatelet response, ex vivo clopidogrel response was measured using the VerifyNow® P2Y12 Assay. The primary endpoint was the 90-day incidence of adverse vascular events including ischemic stroke. Results: A total of 229 patients were included. The median age was 57 years (IQR: 49–64), and 158 (69.00%) were female. Eighty-one (35.37%) patients carried at least one CYP2C9 loss-of-function (LOF) allele. After adjustment for stroke risk factors, the 90-day incidence of ischemic stroke was significantly lower in the LOF group compared to the wild type group (1.23% vs 10.14%; ORadj = 0.16, 95% CI: 0.03–0.91; p = 0.04). Conclusions: Our results suggest protection against ischemic stroke in carriers of CYP2C9*2 or *3 polymorphisms undergoing neurointervention. Our findings warrant further studies to investigate the mechanisms by which CYP2C9 may influence the risk of ischemic stroke.

Original languageEnglish
Article number104901
Number of pages8
JournalJournal of Stroke and Cerebrovascular Diseases
Volume29
Issue number8
DOIs
Publication statusPublished - 1 Aug 2020

Keywords

  • Antiplatelet
  • Clopidogrel
  • CYP2C9
  • Endovascular
  • Ischemia
  • Neurointervention
  • Stroke

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