Interleukin-1β and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures

Abstract

Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen.We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions –31 (C/T), and –511 (C/T) of interleukin-1beta (IL-1β) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1β to assess its relation to such polymorphisms.This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1β promoter at positions −31 (C/T), −511 (C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1β-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68–9.5; P = 0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18–2.3; P = 0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78–9.15; P = 0.001and OR: 1.73; 95% CI: 1.24–2.4; P = 0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1–12.5 for the IL-1 RA II/II genotype; P = 0.001) and (OR: 1.94; 95% CI: 1.3–2.8 for the allele II; P = 0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1β compared with those with other genotypes and alleles.We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1β promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.

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

“…The IL-1β-31 variant involves a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro 25. T allele of IL-1β-511 reportedly up-regulates promotor activity, consequently increasing IL-1β production both in vitro and in vivo 926. The present study found near-complete LD between IL-1β-31 and IL-1β-511 variants, similar to a study of adult gastric cancer 25.…”

Aetiology of febrile seizures – a problem not fully understood

“…The interleukin 1 receptor antagonist (IL-1RA), controlling the IL-1, is an anti-inflammatory protein. Studies indicate a relationship between the overexpression of IL-1β and an imbalance between IL-1β and IL-1RA and FS (20)(21)(22) . Increased IL-1 and tumour necrosis factor (TNF) levels in response to exogenous pyrogens stimulate an increase in the levels of interleukin 6 (IL-6).…”

Functional Nutrients for Epilepsy

“…Little has been reported with respect to inflammatory cytokines and enzymes. However, two papers investigating single-nucleotide polymorphisms of interleukin 1β (IL-1β) in patients with febrile seizures have raised the possibility of de novo mutations [86,87]. They found that IL-1β TT genotypes were over-represented in febrile seizure–experiencing groups compared with healthy controls.…”