Skip to main content
Log in

Interleukin-1 receptor antagonist and interleukin-1β-511 gene polymorphisms among Egyptian children with febrile seizures

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

Febrile seizures (FSs) are the most common form of childhood seizures. The higher levels of pro-inflammatory cytokines in children may induce seizures, and alternatively, higher levels of anti-inflammatory cytokines may act as a defense mechanism against seizures. We aimed to investigate whether interleukin (IL)-1β-511 C/T (pro-inflammatory cytokine) (rs16944) and IL-1 receptor antagonist (IL-1Ra) (an anti-inflammatory cytokine) gene polymorphisms could be used as markers for prediction of susceptibility to FSs. The current study included 22 patients with FSs and 22 normal control subjects. All patients were subjected to thorough history taking, full neurological examination, electroencephalography, and peripheral blood sampling for genotype analyses. Detection of IL-1Ra gene polymorphisms was done using polymerase chain reaction (PCR), while a restriction fragment length polymorphism analysis of the PCR products was used for the detection of IL-1β-511 C/T gene polymorphisms. The mean age of onset of first febrile seizures was 15.7 months. Eighteen (81.8 %) cases had the criteria of complex FSs. Frequencies of alleles C and T for IL-1β-511 were 26/44 and 18/44, respectively, in FS patients and 22/44 for both in the control subjects. The CC genotype was significantly more common in the FS patients than in the control group. The IL-1Ra-I homozygote was more frequent in patients with FSs than in healthy controls. The IL-1Ra homozygous I/I and IL-1β-511 CC gene polymorphisms are associated with a higher susceptibility to febrile seizures, which may be useful markers for predicting the development of febrile seizures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Addas-Carvalho M, Origa AF, Saad ST (2004) Interleukin-1beta and tumor necrosis factor levels in stored platelet concentrates and the association with gene polymorphisms. Transfusion 44(7):996–1003

    Article  CAS  PubMed  Google Scholar 

  • Berkovic SF, Howell RA, Hay DA, Hopper JL (1998) Epilepsies in twins: genetics of the major epilepsy syndromes. Ann Neurol 43:435–445

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Wilkins LM, Aziz N, Cannings C et al (2006) Single nucleotide polymorphisms in the human interleukin-1B gene affect transcription according to haplotype context. Hum Mol Genet 15:519–529

    Article  CAS  PubMed  Google Scholar 

  • Chou CI, Lin WD, Wang CH, Tsai CH, Li TC, Tsai FJ (2010) Interleukin (IL)-1b, IL-1 receptor antagonist, IL-6, IL-8, IL-10, and tumor necrosis factor a gene polymorphisms in patients with febrile seizures. J Clin Lab Anal 24:154–159

    Article  CAS  PubMed  Google Scholar 

  • Haspolat S, Mihci E, Cosxkun M, Gumuslu S, Ozben T, Yegin O (2002) Interleukin 1b, tumor necrosis factor-a, and nitrite levels in febrile seizures. J Child Neurol 17:749–751

    Article  PubMed  Google Scholar 

  • Haspolat S, Baysal Y, Duman O, Coskun M, Tosun O, Yegin O (2005) Interleukin-1a, interleukin-1b, and interleukin-1Ra polymorphisms in febrile seizures. J Child Neurol 20:565–568

    PubMed  Google Scholar 

  • Hauser WA (1994) The prevalence and incidence of convulsive disorders in children. Epilepsia 35(Suppl. 2):S1–S6

    Article  PubMed  Google Scholar 

  • Kamikawa H, Hori T, Nakane H, Aou S, Tashiro N (1998) IL-1beta increases norepinephrine level in rat frontal cortex: involvement of prostanoids, NO, and glutamate. Am J Physiol 275:R803–R810

    CAS  PubMed  Google Scholar 

  • Kauffman MA, Moron DG, Consalvo D, Bello R, Kochen S (2008) Association study between interleukin-1 gene and epileptic disorders: a HuGe review and meta-analysis. Genet Med 10(2):83–88

    Article  CAS  PubMed  Google Scholar 

  • Kira R, Torisu H, Takemoto M, Nomura A, Sakai Y, Sanefuji M et al (2005) Genetic susceptibility to simple febrile seizures: interleukin-1beta promoter polymorphisms are associated with sporadic cases. Neurosci Lett 384:239–244

    Article  CAS  PubMed  Google Scholar 

  • Kira R, Ishizaki Y, Torisu H, Sanefuji M, Takemoto M, Sakamoto K, Matsumoto S, Yamaguchi Y, Yukaya N, Sakai Y, Gondo K, Hara T (2010) Genetic susceptibility to febrile seizures: case–control association studies. Brain Dev 32:57–63

    Article  PubMed  Google Scholar 

  • Matsuo M, Sasaki K, Ichimaru T, Nakazato S, Hamasaki Y (2006) Increased IL-1β production from dsRNA-stimulated leukocytes in febrile seizures. Pediatr Neurol 35(2):102–106

    Article  PubMed  Google Scholar 

  • Santilla S, Savinainen K, Hurme M (1998) Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1 β production in vitro. Scand J Immunol 47:195–198

    Article  Google Scholar 

  • Serdaroglu GS, Alpman A, Tosun A, Pehlıvan S, Zkınay FO, Tekgul H, Gokben S (2009) Febrile seizures: interleukin 1β and interleukin-1 receptor antagonist polymorphisms. Pediatr Neurol 40:113–116

    Article  PubMed  Google Scholar 

  • Shahin MHA, Khalifa SI, Gongf Y, Lamiaa N, Hammad LN, Sallam MTH, El Shafeyd M, Alid SS, Mohamed-Eslam FM-E, Langaee MT, Johnson JA (2011) Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. Pharmacogenet Genom 21(3):130–135. doi:10.1097/FPC.0b013e3283436b86

    Article  CAS  Google Scholar 

  • Tilgen N, Pfeiffer H, Cobilanschi J, Rau B, Horvath S, Elger CE, Propping P, Heils A (2002) Association analysis between the human interleukin 1beta (−511) gene polymorphism and susceptibility to febrile convulsions. Neurosci Lett 334:68–70

    Article  CAS  PubMed  Google Scholar 

  • Tsai FJ, Hsieh YY, Chang CC, Lin CC, Tsa CH (2002) Polymorphisms for interleukin 1-β exon 5 and interleukin 1 receptor antagonist in Taiwanese children with febrile convulsions. Arch Pediatr Adolesc Med 156:545–548

    Article  PubMed  Google Scholar 

  • Tsuboi T, Endo S (1991) Genetic studies of febrile convulsions: analysis of twin and family data. Epilepsy Res Suppl 4:119–128

    CAS  PubMed  Google Scholar 

  • Tutuncuoglu S, Kutukculer N, Kepe L, Coker C, Berdeli A, Tekgul H (2001) Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions. Pediatr Int 43:235–239

    Article  CAS  PubMed  Google Scholar 

  • Virta M, Hurme M, Helminen M (2002) Increased frequency of interleukin-1beta (−511) allele 2 in febrile seizures. Pediatr Neurol 26:192–195

    Article  PubMed  Google Scholar 

  • Wang S, Cheng Q, Malik S, Yang J (2000) Interleukin-1beta inhibits gamma-aminobutyric acid type A (GABA (A)) receptor current in cultured hippocampal neurons. J Pharmacol Exp Ther 292:497–504

    CAS  PubMed  Google Scholar 

  • Wen AQ, Wang J, Feng K, Zhu PF et al (2006) Effects of haplotypes in the interleukin 1beta promoter on lipopolysaccharide-induced interleukin 1beta expression. Shock 26:25–30

    Article  CAS  PubMed  Google Scholar 

  • Wu ZQ, Sun L, Sun Y-H, Ren C, Jiang Y-H, Lv X-L (2012) Interleukin 1 beta −511 C/T gene polymorphism and susceptibility to febrile seizures: a meta-analysis. Mol Biol Rep 39:5401–5407

    Article  CAS  PubMed  Google Scholar 

  • Zeise ML, Espinoza J, Morales P, Nalli A (1997) Interleukin-1beta does not increase synaptic inhibition in hippocampal CA3 pyramidal and dentate gyrus granule cells of the rat in vitro. Brain Res 768:341–344

    Article  CAS  PubMed  Google Scholar 

  • Zhang D, Zheng H, Zhou Y, Tang X, Yu B, Li J (2007) Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer. BMC Cancer 7:45. doi:10.1186/1471-2407-7-45

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

The author(s) declared no conflicts of interest with respect to the authorship and/or publication of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hoiyda A. Abdel Rasol.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdel Rasol, H.A., Issac, M.S.M., Abdel Ghaffar, H. et al. Interleukin-1 receptor antagonist and interleukin-1β-511 gene polymorphisms among Egyptian children with febrile seizures. Comp Clin Pathol 23, 419–425 (2014). https://doi.org/10.1007/s00580-012-1635-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-012-1635-y

Keywords

Navigation