title: Interleukin-1β and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures: A case-control study.
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.
authors.affiliation: Department of Pediatrics Department of Pediatrics, Faculty of Medicine, Cairo University Department of Pediatrics, Faculty of Medicine, Aswan University Department of Clinical pathology Department of Microbiology and Immunology Department of Internal Medicine, Faculty of Medicine, Zagazig University, Egypt.
authors.forename: Salah
authors.initials: S
authors.lastname: Al Morshedy
authors.forename: Hosam F
authors.initials: HF
authors.lastname: Elsaadany
authors.forename: Hany E
authors.initials: HE
authors.lastname: Ibrahim
authors.forename: Ashraf M
authors.initials: AM
authors.lastname: Sherif
authors.forename: Mohsen A A
authors.initials: MAA
authors.lastname: Farghaly
authors.forename: Mayy A N
authors.initials: MAN
authors.lastname: Allah
authors.forename: Heba
authors.initials: H
authors.lastname: Abouzeid
authors.forename: Shaimaa S A
authors.initials: SSA
authors.lastname: Elashkar
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Hamed
authors.forename: Manar M
authors.initials: MM
authors.lastname: Fathy
authors.forename: Atef M
authors.initials: AM
authors.lastname: Khalil
authors.forename: Maha A
authors.initials: MA
authors.lastname: Noah
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Hegab
authors.forename: Ahmed R
authors.initials: AR
authors.lastname: Ahmed
authors.forename: Mustafa I A
authors.initials: MIA
authors.lastname: Hashem
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Emam
authors.forename: Heba G
authors.initials: HG
authors.lastname: Anany
authors.forename: Boshra R
authors.initials: BR
authors.lastname: Ibrahim
authors.forename: Heba H
authors.initials: HH
authors.lastname: Gawish
authors.forename: Rehab M
authors.initials: RM
authors.lastname: Nabil
authors.forename: Lobna Abdel
authors.initials: LA
authors.lastname: Fattah
authors.forename: Salah F
authors.initials: SF
authors.lastname: Alsayed
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004534:Egypt / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D003294:Seizures, Febrile / Q000235:genetics*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta