CYP2C19 Pleomorphisms on Stroke Recurrence in a Southeast Asian Population
Jia Dong James Wang1, Huilian Carol Tham2
1Lee Kong Chian School of Medicine, 2National Neuroscience Institute
Objective:

This study aims to characterize if differences in CYP2C19 genotype would lead to higher odds of long-term reoccurrence of ischemia stroke in stroke patients in an Asian cohort whereby pleomorphisms are more common. 

Background:

Clopidogrel is an anti-platelet utilised for secondary prevention of strokes. However, clopidogrel is a pro-drug activated in the liver, with current evidence showing variability in its anti-platelet effect due to differences in metabolism, notably by CYP2C19

Design/Methods:

This retrospective study included 268 consecutive patients with first-time ischaemic stroke. Data from subjects were collected from their outpatient visits and hospital database up to 31 October 2017 and retrospectively analysed after follow-up for seven years. A multivariate cox regression test was performed to assess overall risk of stroke recurrence for each genotype with correction for significant factors like age and hypertension. 

Results:

Only reoccurrence of stroke in the second and third year were significant, HR 0.335 (CI 0.123-0.911), HR 0.396 (CI 0.162-0.968) respectively with p<0.05. For reoccurrence of strokes beyond the 4th year or the cumulative reoccurrence of strokes, clopidogrel resistance was statistically insignificant (p>0.05).

Conclusions:

Loss of function allele of CY2C19 was associated with increased reoccurrence of stroke in the second and third year due to reduced anti-platelet effect. Therefore, it is advisable to genotype these patients. However, CY2C19 genotype was not associated with increased risk of reoccurrence of stroke in the long-term. This was likely to occur due to other compensatory mechanisms and more important co-morbidities like hypertension, reducing the need to genotype such patients. 

10.1212/WNL.0000000000210803
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