Choi Jieun, Choi Sun Ah, Kim Soo Yeon, Kim Hunmin, Lim Byung Chan, Hwang Hee, Chae Jong Hee, Kim Ki Joong, Oh Sohee, Kim Eun Young, Shin Jeon Soo
Department of Pediatrics, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Department of Pediatrics, Dankook University Hospital, Cheonan, Korea.
J Clin Neurol. 2019 Oct;15(4):555-563. doi: 10.3988/jcn.2019.15.4.555.
Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1β, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+.
Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1β-31 (rs1143627), IL-1β-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1β, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed.
Near-complete linkage disequilibrium exists between IL-1β-31 and IL-1β-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1β levels than were CC+TT genotypes in FS (both <0.05). CT genotypes of IL-1β-31 and IL-1β-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1β levels after AFS for CT genotypes of IL-1β-31 and IL-1β-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1.
Genetic variants located in IL-1β-31 and IL-1β-511 promotor regions are correlated with higher postictal IL-1β levels in FS. These results suggest that IL-1 gene cluster variants in IL-1β-31 and IL-1β-511 are a host genetic factor for provoking FS in Korean children.
热性惊厥（FS）是一种仅在儿童期发生的特殊类型惊厥。伴有热性惊厥附加症的全面性癫痫（GEFS+）是一种与FS和无热惊厥（AFS）相关的家族性癫痫综合征。两种惊厥类型均与发热有关，但炎症的遗传易感性是否与之相关仍不清楚。旨在分析FS和GEFS+患者发作后血清细胞因子水平与细胞因子基因白细胞介素（IL）-1β、IL-6和高迁移率族蛋白B1（HMGB1）基因变异之间的关联。
采用SNaPshot分析法对208名受试者（57例FS患者、43例GEFS+患者和108名对照）进行IL-1β-31（rs1143627）、IL-1β-511（rs16944）、IL-6-572（rs1800796）和HMGB1 3814（rs2249825）基因分型。仅对68例患者（38例FS、10例GEFS+和20名对照）在惊厥发作后2小时内使用酶联免疫吸附测定法分析血清IL-1β、IL-6和HMGB1水平。分析等位基因分布、基因型分布以及与血清细胞因子水平的相关性。
IL-1β-31和IL-1β-511变异之间存在近乎完全的连锁不平衡。在FS中，这些变异的CT基因型与发作后血清IL-1β水平显著高于CC+TT基因型（均<0.05）。IL-1β-31和IL-1β-511变异的CT基因型与FS的相关性比CC+TT基因型更强（优势比分别为1.691和1.731）。对于GEFS+，IL-1β-31和IL-1β-511的CT基因型在AFS后的血清IL-1β水平也高于CC+TT基因型。未发现IL-6和HMGB1有显著关联。
位于IL-1β-31和IL-1β-511启动子区域的基因变异与FS发作后较高的IL-1β水平相关。这些结果表明，IL-1β-31和IL-1β-511中的IL-1基因簇变异是韩国儿童引发FS的宿主遗传因素。
