Association between CYP2C9 polymorphisms and ischemic stroke following endovascular neurointervention

被引:4
作者
Sreedharan, Subhashaan [1 ,2 ]
Churilov, Leonid [3 ]
Chan, Jianxiong [2 ,9 ]
Todaro, Marian [2 ,4 ,9 ]
Coulthard, Alan [7 ,8 ]
Hocking, Jeffrey [7 ,8 ]
Mahady, Kate [7 ,8 ]
Mitchell, Peter [5 ,6 ]
Dowling, Richard [5 ,6 ]
Bush, Steven [5 ,6 ]
Kwan, Patrick [1 ,2 ,4 ,9 ,10 ]
Yan, Bernard [1 ,2 ,4 ,5 ]
机构
[1] Royal Melbourne Hosp, Melbourne Brain Ctr, Parkville, Vic 3050, Australia
[2] Univ Melbourne, Dept Med, Parkville, Vic 3050, Australia
[3] Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic 3084, Australia
[4] Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3050, Australia
[5] Royal Melbourne Hosp, Dept Radiol, Parkville, Vic 3050, Australia
[6] Univ Melbourne, Dept Radiol, Parkville, Vic 3050, Australia
[7] Royal Brisbane & Womens Hosp, Dept Med Imaging, Herston, Qld 4029, Australia
[8] Univ Queensland, Acad Discipline Med Imaging, Brisbane, Qld 4072, Australia
[9] Monash Univ, CCS, Dept Neurosci, Melbourne, Vic 3004, Australia
[10] Alfred Hlth, Dept Neurol, Melbourne, Vic 3004, Australia
关键词
CYP2CP; Endovascular; Ischemia; Neurointervention; Stroke; Clopidogrel; Antiplatelet; CYTOCHROME P4502C9; CYP2C9-ASTERISK-3; ALLELES; RISK-FACTORS; CLOPIDOGREL; VARIABILITY; INHIBITION; CYP2C19-ASTERISK-2; RESPONSIVENESS; THROMBOSIS; GENOTYPE;
D O I
10.1016/j.jstrokecerebrovasdis.2020.104901
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 (R) 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 themechanisms by which CYP2C9 may influence the risk of ischemic stroke.
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页数:8
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