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与白细胞介素-1β血清水平相关的白细胞介素-1B rs16944(T/C)多态性影响缺血性中风患者的癫痫易感性。

Polymorphism of IL-1B rs16944 (T/C) associated with serum levels of IL-1β affects seizure susceptibility in ischemic stroke patients.

作者信息

Ma Xiaojun, Sun Liangwei, Li Xiaoli, Xu Yanlu, Zhang Qingyan

机构信息

Department of Geriatrics, Shandong Provincial Third Hospital, Jinan, China.

Department of Neurology, Shandong Provincial Third Hospital, Jinan, China.

出版信息

Adv Clin Exp Med. 2023 Jan;32(1):23-29. doi: 10.17219/acem/152738.

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.

MATERIAL 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.

摘要

背景

中风后癫痫发作及随后癫痫的发生不仅可能阻碍患者康复,还会增加并发症风险。白细胞介素(IL)-1β已被证明在缺血性中风后会急性上调,并在缺血性中风患者首次癫痫发作后的癫痫复发中起作用。同时,编码IL-1β的IL-1B基因变体与热性惊厥的诱发有关。

目的

研究IL-1B基因的5种多态性与缺血性中风患者癫痫易感性的潜在关联,并探讨可能的机制。

材料与方法

总共856例缺血性中风患者被分为对照组(无中风后癫痫发作的患者)和病例组(有中风后癫痫发作的患者)。使用TaqMan SNP基因分型检测法检测IL-1B基因多态性rs10490571(T/C)、rs114363(C/T)、rs1143623(G/C)、rs16944(T/C)和rs2853550(A/G),并使用酶联免疫吸附测定(ELISA)测量血清IL-1β水平。收集入院时的人口统计学数据、临床特征和脑血管疾病危险因素。进行多变量分析以确定独立关联,并使用方差分析(ANOVA)及事后检验比较IL-1β水平。

结果

74例患者(8.6%,74/856)在中风发作后1年内出现中风后癫痫发作。多变量分析显示,在调整了中风侧别、溶栓治疗、他汀类药物使用和IL-1B rs10490571后,IL-1B的rs16944多态性、皮质受累情况和入院时的美国国立卫生研究院卒中量表(NIHSS)评分与中风后癫痫发作相关。与CC基因型相比,IL-1B rs16944 TT(比值比(OR):1.923,95%置信区间(95%CI):1.257 - 4.185)和TC基因型(OR:1.469,95%CI:1.130 - 2.974)与中风后癫痫发作风险显著增加相关。对IL-1β水平进行的单因素方差分析表明,TT>TC>CC基因型的水平有升高趋势(分别为6.41、4.53和2.10 pg/mL)。

结论

IL-1B rs16944多态性与缺血性中风后的癫痫易感性存在独立关联。其机制可能与IL-1β水平的调节有关。

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