The association between CYP2C19 genotype and of in-stent restenosis among patients with vertebral artery stent treatment

Aims: Preventing stroke through endovascular treatment with vertebral artery stent remains a great challenge due to the occurrence of an in-stent restenosis.

Materials & methods: In this study, a retrospective analysis was conducted in 90 patients who had been treated with VAS between 2004 and 2011 in Nanjing Drum Tower Hospital. Patients were followed up at 3 months, 6 months,and 1 year after VAS treatment and annually thereafter. For each time point, neurological function tests, vessel ultrasound and computer tomography angiography were performed to preliminarily screen the vessel stenosis. Digital subtraction angiography was used to verify the narrow sign on CTA or ultrasound. Clinical features of each patient including clopidogrel metabolization genes (CYP2C19, CYP3A4, and P2Y12) were recorded with purpose to investigate the possible risk factors for the development of ISR.

Results: Single factor analysis dem-onstrated that hyperlipidemia (P < 0.05) and CYP2C19 (P < 0.01) loss-of-function geno-type increased the likelihood of ISR. A multiple logistic cox regression analysis also showed that stroke patients with hyperlipidemia (HR 3.719, 95% CI: 1.094-12.637, P = 0.035), and CYP2C19 loss-of-function genotype (HR 2.959, 95% CI: 1.325-6.610, P = 0.008) were more likely to suffer from ISR. Furthermore, CYP2C19 alleles were mainly divided into three groups: wt/wt (CYP2C19 *1/*1), wt/m (CYP2C19 *1/*2 and *1/*3), and m/m (CYP2C19 *2/*2,*2/*3 and*3/*3). Recurrent rate of ischemic stroke in m/m and wt/m groups was higher than the wt/wt group (OR: 0.141, 95% CI: 0.016-1.221, P = 0.042).

Conclusion: The study leads to the conclusion that hyperlipidemia and CYP2C19 impotency are possible risk factors for the development of ISR in VAS-treated patients with ischemic. Moreover, VAS-treated patients with CYP2C19 impotency were susceptible to recurrent stroke during our 54-month follow-up.