title: Genetic susceptibility to simple febrile seizures: interleukin-1beta promoter polymorphisms are associated with sporadic cases.
abstract: Febrile seizures (FSs) are the commonest form of convulsions. A genetic predisposition to FSs is known, based on family studies, twin studies, and complex segregation analysis. Simple FSs may be more homogenous in their clinical manifestations, and show better agreement with the multifactorial inheritance theory than the complex type. Interleukin-1 (IL-1) beta is one of the pro-inflammatory cytokines that are postulated to be involved in the development of FSs. To determine whether or not function-related polymorphisms of the IL-1beta (IL1B) gene are associated with susceptibility to simple FSs, the genotypes for two biallelic polymorphisms in the promoter region at positions -31 and -511 of the IL1B gene were determined by means of PCR-restriction fragment length polymorphism in 229 FS patients (108 sporadic and 60 familial simple FS, and 61 complex FS patients) and 158 controls. IL1B -31C/T, a TATA box polymorphism, has been found to be in complete linkage disequilibrium with the IL1B -511C/T polymorphism. Sporadic simple FS patients exhibited significantly higher frequencies of IL1B -31C/-511T alleles and homozygotes than controls (uncorrected p = 0.0094 and 0.0029, corrected p = 0.038 and 0.035, respectively), while no differences were observed in patients with all or familial simple FSs versus controls. There were no significant differences in the frequencies of -31C/T and -511C/T in the IL-1beta promoter gene between complex FS patients and controls. The present study suggests that the IL-1beta gene contributes to a genetic susceptibility to the development of simple FSs of sporadic occurrence.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. kirari@pediatr.med.kyushu-u.ac.jp
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Torisu
authors.forename: Megumi
authors.initials: M
authors.lastname: Takemoto
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nomura
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Sakai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sanefuji
authors.forename: Kanji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Gondo
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D007375:Interleukin-1 / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D003294:Seizures, Febrile / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007375:Interleukin-1