Polymorphism of IL-1Brs16944 (T/C) associated with serum levels of IL-1β affects seizure susceptibility in ischemic stroke patients

Abstract

Background. Seizures and the subsequent development of epilepsy after stroke may not only hinder patient’s recovery but also increase the risk of complications. Interleukin (IL)-1β has been shown to be acutely upregulated after ischemic stroke and play a role in the recurrence of seizures following the first epileptic seizure in patients suffering an ischemic stroke. Meanwhile, variants of the IL-1B gene encoding IL-1β are involved in the stimulation of febrile seizures. Objectives. To study the potential associations of the 5 polymorphisms of the IL-1B gene with seizure susceptibility in ischemic stroke patients, and to explore the possible mechanisms. Materials and methods. A total of 856 ischemic stroke patients were allocated into the control group (patients without post-stroke seizures) and the case group (patients with post-stroke seizures). The IL-1B polymorphisms rs10490571 (T/C), rs114363 (C/T), rs1143623 (G/C), rs16944 (T/C), and rs2853550 (A/G) were detected using TaqMan SNP genotyping assays, and serum IL-1β levels were measured using the enzyme-linked immunosorbent assay (ELISA). Demographic data, clinical characteristics and cerebrovascular disease risk factors at admission were collected. Multivariate analysis was performed to determine independent associations, and IL-1β levels were compared using analysis of variance (ANOVA) followed by a post hoc test. Results. In 74 patients (8.6%, 74/856), post-stroke seizures occurred within 1 year of stroke onset. The multivariate analysis showed that the rs16944 polymorphism of IL-1B, cortical involvement and National Institutes of Health Stroke Scale (NIHSS) score on admission were correlated with post-stroke seizures after adjusting for stroke laterality, thrombolysis, use of statins, and IL-1B rs10490571. The IL-1B rs16944 TT (odds ratio (OR): 1.923, 95% confidence interval (95% CI): 1.257–4.185) and TC genotypes (OR: 1.469, 95% CI: 1.130–2.974) were associated with a significantly increased risk of post-stroke seizures compared to the CC genotype. One-way ANOVA for IL-1β levels demonstrated a tendency for higher levels in TT > TC > CC genotypes (6.41 compared to 4.53 compared to 2.10 pg/mL, respectively). Conclusions. The IL-1B rs16944 polymorphism had an independent association with seizure susceptibility after ischemic stroke. The mechanism might be associated with the regulation of IL-1β levels.