1. Association between CYP2C9 polymorphisms and ischemic stroke following endovascular neurointervention.
- Author
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Sreedharan S, Churilov L, Chan J, Todaro M, Coulthard A, Hocking J, Mahady K, Mitchell P, Dowling R, Bush S, Kwan P, and Yan B
- Subjects
- Aged, Brain Ischemia diagnosis, Clopidogrel pharmacokinetics, Cytochrome P-450 CYP2C9 metabolism, Female, Humans, Male, Middle Aged, Pilot Projects, Platelet Aggregation Inhibitors pharmacokinetics, Prospective Studies, Protective Factors, Queensland, Risk Assessment, Risk Factors, Stroke diagnosis, Time Factors, Treatment Outcome, Victoria, Brain Ischemia genetics, Brain Ischemia prevention & control, Cerebrovascular Disorders therapy, Cytochrome P-450 CYP2C9 genetics, Endovascular Procedures adverse effects, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Stroke genetics, Stroke prevention & control
- 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® P2Y
12 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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