Acta Medica Iranica 2017. 55(6):354-359.

Association of the Single Nucleotide Polymorphisms of the Genes Encoding IL-2 and IFN-γ With Febrile Seizure
Amin Shahrokhi, Ameneh Zare-Shahabadi, Mohammad Naeimi Poor, Firouzeh Sajedi, Samaneh Soltani, Samaneh Zoghi, Reza Shervin Badv, Mahmoud Reza Ashrafi, Nima Rezaei


Inflammatory elements and genetics have major roles in febrile seizures (FS) pathogenesis. Seventy patients were enrolled and compared with 139 controls. The allele and genotype frequency of the IL-2 gene at -330 and +166 positions and the IFN-γ at +874 position were determined. A significant positive association with GG genotype at position -330 in the patient group was found (P=0.003). Further, a positive association was detected in simple and complex FS groups at the same position (P=0.03, P=0.004). IL-2 GT haplotype was significantly more common in the patients compared to controls (P=0.0008). Higher frequency of GT haplotype was detected in simple FS patients in comparison to controls (P=0.0003). Contrary, IL-2 TG haplotype frequency was lower in complex FS group (P=0.005). Overrepresentation of certain alleles, genotypes and haplotypes in IL-2 gene in FS patients could predispose individuals to this disease.


Febrile seizure; Gene polymorphisms; Interleukin-2; IFN-γ; Etiology

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Szelényi J. Cytokines and the central nervous system. Brain research bulletin. 2001;54(4):329-38.

Rao R, Prakash A, Medhi B. Role of different cytokines and seizure susceptibility: A new dimension toward epilepsy research. Indian journal of experimental biology. 2009;47(8):625.

Vezzani A. Inflammation and epilepsy. Epilepsy Currents. 2005;5(1):1-6.

Vestergaard M, Basso O, Henriksen TB, Østergaard JR, Olsen J. Risk factors for febrile convulsions. Epidemiology. 2002;13(3):282-7.

Millichap JG. STUDIES IN FEBRILE SEIZURES I. Height of Body Temperature as a Measure of the Febrile-seizure Threshold. Pediatrics. 1959;23(1):76-85.

Serdaroğlu G, Alpman A, Tosun A, Pehlıvan S, Özkınay F, Tekgül H, et al. Febrile seizures: interleukin 1β and interleukin-1 receptor antagonist polymorphisms. Pediatric Neurology. 2009;40(2):113-6.

Nakayama J, Arinami T. Molecular genetics of febrile seizures. Epilepsy research. 2006;70:190-8.

Shahrokhi A, Zare-Shahabadi A, Soltani S, Ashrafi MR, Zoghi S, Hosseini SA, et al. Association of IL6 single nucleotide polymorphisms with febrile seizures. J Neurol Sci. 2014 Jul 15;342(1-2):25-8.

Tsai F-J, Chou I, Hsieh Y-Y, Lee C-C, Lin C-C, Tsai C-H. Interleukin-4 intron 3 polymorphism is not related to susceptibility to febrile seizures. Pediatric Neurology. 2002;27(4):271-4.

Mahyar A, Ayazi P, Orangpour R, Daneshi-Kohan MM, Sarokhani HR, Javadi A, et al. Serum interleukin-1 β and tumor necrosis factor-α in febrile seizures: Is there a link? Korean Journal of Pediatrics. 2014.

Rasol HAA, Issac MSM, Ghaffar HA, El-Mously S. Interleukin-1 receptor antagonist and interleukin-1β-511 gene polymorphisms among Egyptian children with febrile seizures. Comparative Clinical Pathology. 2014;23(2):419-25.

Zare-shahabadi A, Soltani S, Ashrafi MR, Shahrokhi A, Zoghi S, Pourakbari B, et al. Association of IL4 Single-Nucleotide Polymorphisms With Febrile Seizures. Journal of child neurology. 2014:0883073814551389.

Sinha S, Patil S, Jayalekshmy V, Satishchandra P. Do cytokines have any role in epilepsy? Epilepsy research. 2008;82(2):171-6.

Choi J, Min HJ, Shin J-S. Increased levels of HMGB1 and pro-inflammatory cytokines in children with febrile seizures. J Neuroinflammation. 2011;8(135):884-0276.

Shahrokhi A, Zare-Shahabadi A, Soltani S, Soleimani F, Vameghi R, Konjkav AR, et al. Association of TGFB, but not IL10, Single Nucleotide Polymorphisms with Febrile Seizures. Seizure. 2015.

Zare-Shahabadi A, Ashrafi MR, Shahrokhi A, Soltani S, Zoghi S, Soleimani F, et al. Single nucleotide polymorphisms of TNF-Α gene in febrile seizures. Journal of the neurological sciences. 2015.

Soltani S, Zare-Shahabadi A, Shahrokhi A, Rezaei A, Zoghi S, Zamani GR, et al. Association of Interleukin-1 Gene Cluster and Interleukin-1 Receptor Polymorphisms With Febrile Seizures. Journal of child neurology. 2015:0883073815610429.

Amirzargar AA, Naroueynejad M, Khosravi F, Dianat SS, Rezaei N, Mytilineos J, et al. Cytokine single nucleotide polymorphisms in Iranian populations. European cytokine network. 2008 Jun;19(2):104-12.

Rizzi M, Perego C, Aliprandi M, Richichi C, Ravizza T, Colella D, et al. Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development. Neurobiology of disease. 2003;14(3):494-503.

Ravizza T, Vezzani A. Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system. Neuroscience. 2006;137(1):301-8.

De Simoni MG, Perego C, Ravizza T, Moneta D, Conti M, Marchesi F, et al. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. European Journal of Neuroscience. 2000;12(7):2623-33.

Virta M, Hurme M, Helminen M. Increased Plasma Levels of Pro‐and Anti‐inflammatory Cytokines in Patients with Febrile Seizures. Epilepsia. 2002;43(8):920-3.

Kira R, Torisu H, Takemoto M, Nomura A, Sakai Y, Sanefuji M, et al. Genetic susceptibility to simple febrile seizures: interleukin-1β promoter polymorphisms are associated with sporadic cases. Neuroscience letters. 2005;384(3):239-44.

Tsai F-J, Hsieh Y-Y, Chang C-C, Lin C-C, Tsai C-H. Polymorphisms for Interleukin 1 {beta} Exon 5 and Interleukin 1 Receptor Antagonist in Taiwanese Children With Febrile Convulsions. Archives of pediatrics & adolescent medicine. 2002;156(6):545.

Tilgen N, Pfeiffer H, Cobilanschi J, Rau B, Horvath S, Elger CE, et al. Association analysis between the human interleukin 1β (− 511) gene polymorphism and susceptibility to febrile convulsions. Neuroscience letters. 2002;334(1):68-70.

Sander T, Schulz H, Saar K, Gennaro E, Riggio MC, Bianchi A, et al. Genome search for susceptibility loci of common idiopathic generalised epilepsies. Human molecular genetics. 2000;9(10):1465-72.

Straussberg R, Amir J, Harel L, Punsky I, Bessler H. Pro-and anti-inflammatory cytokines in children with febrile convulsions. Pediatric Neurology. 2001;24(1):49-53.


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