title: Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS.
abstract: Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p=0.0067), and A allele at rs4251981 in 5' upstream of IL1RN with borderline significance (p=0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40-10.8, p=0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p=0.011). We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.
authors.affiliation: Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan. Electronic address: makisaito-tky@umin.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Saitoh
authors.affiliation: Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Special Needs Education, Graduate School of Education, Okayama University, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Ohmori
authors.affiliation: Department of Pediatrics, Ohta Nishinouchi General Hospital, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Ohta Nishinouchi General Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Child Medical Center, Osaka City General Hospital, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Pediatrics, Child Medical Center, Osaka City General Hospital, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Horino
authors.affiliation: Department of Pediatrics, Kishiwada City Hospital, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohmura
authors.affiliation: Department of Pediatrics, Kitano Hospital, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kumakura
authors.affiliation: Division of Neurology, Nagano Childrens' Hospital, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Division of Neurology, Nagano Childrens' Hospital, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hirabayashi
authors.affiliation: Department of Pediatrics, Yamaguchi University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kajimoto
authors.affiliation: Department of Pediatrics, Sendai City, Hospital, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Pediatrics, Niigata City Hospital, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Department of Neurology, Gunma Children's Medical Center, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shiihara
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kasai
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Terashima
authors.affiliation: Division of Neurology, National Center for Child Health and Development, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizuguchi
mesh_terms: D001927:Brain Diseases / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D004828:Epilepsies, Partial / Q000150:complications; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D003294:Seizures, Febrile / Q000150:complications; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D016207:Cytokines; D015222:Sodium Channels
keywords: Acute encephalopathy; Association studies in genetics; ILRN; SCN1A; SCN2A