Association Analysis of Interleukin-1β, Interleukin-6, and HMGB1 Variants with Postictal Serum Cytokine Levels in Children with Febrile Seizure and Generalized Epilepsy with Febrile Seizure Plus
10.3988/jcn.2019.15.4.555
- Author:
Jieun CHOI
1
;
Sun Ah CHOI
;
Soo Yeon KIM
;
Hunmin KIM
;
Byung Chan LIM
;
Hee HWANG
;
Jong Hee CHAE
;
Ki Joong KIM
;
Sohee OH
;
Eun young KIM
;
Jeon Soo SHIN
Author Information
1. Department of Pediatrics, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. jechoi66@snu.ac.kr
- Publication Type:Original Article
- Keywords:
interleukin-1β;
interleukin-6;
high mobility group box-1;
febrile seizure;
genelized epilepsy with febrile seizure plus;
variant
- MeSH:
Alleles;
Child;
Enzyme-Linked Immunosorbent Assay;
Epilepsy;
Epilepsy, Generalized;
Fever;
Genetic Predisposition to Disease;
Genotype;
HMGB1 Protein;
Humans;
Inflammation;
Interleukin-1;
Interleukin-6;
Interleukins;
Linkage Disequilibrium;
Multigene Family;
Promoter Regions, Genetic;
Seizures;
Seizures, Febrile
- From:Journal of Clinical Neurology
2019;15(4):555-563
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND AND PURPOSE: 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+. METHODS: 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. RESULTS: 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 p<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. CONCLUSIONS: 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.
