Abstract
BackgroundFebrile seizures are the most common form of childhood seizures. Among pro-inflammatory cytokines, interleukin-6 is the key acute-phase cytokine. To date, only a few studies concerned the association of interleukin-6 gene polymorphisms with febrile seizures.In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions –174 (G/C), –572 (G/C), and –597 (G/A) in the promoter region of the interleukin-6 gene for the first time in Egyptian children with febrile seizures.MethodsThis was a case–control study included 100 patients with febrile seizure, and matched with age, gender, ethnicity 100 healthy control subjects.Interleukin-6 –174 (G/C), −572 (G/C), and −597 (G/A) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL6 levels were measured by ELISA method.ResultsCompared to the controls subjects, the frequency of the −174 GG and −597 GG IL6 genotypes were observed to be increased in children with febrile seizures (OR: 4.17; 95 % CI: 1.86–9.49; P <0.01 and OR: 1.96; 95 % CI: 1.06–3.63;P <0.05, respectively). We found a significant positive association between the −597 GG genotype and susceptibility to complex febrile seizures as did the G allele at the same position (OR: 4.2; 95 % CI: 1.4–13.3 for the GG genotype; P <0.01) and (OR: 2.89; 95 % CI: 1.1–7.7 for the G allele; P <0.05 respectively). Our data revealed no association between IL6- genotypes and serum IL6 levels in patients with febrile seizures (P > 0.05).ConclusionIn conclusion, our data brought a novel observation that the presence of a G allele or GG genotype at the −174 and the GG genotype at the −597 positions of the promoter region of the interleukin-6 gene constitute risk factors for developing febrile seizures in Egyptian children. Moreover, we observed a significant positive association between the IL6 –597 GG genotype and susceptibility to complex febrile seizures as did the G allele at the same position. However, we found no association between IL6- genotypes and serum IL6 levels in patients with febrile seizures.
Highlights
Febrile seizures are the most common form of childhood seizures
We found a significant increase in the frequency of the G allele (OR: 1.84; 95 % confidence interval (CI): 1.21–2.8; P
We found a significant positive associations between febrile seizure and the interleukin6 G allele at the −174 position (OR: 1.84; P
Summary
Febrile seizures are the most common form of childhood seizures. Among pro-inflammatory cytokines, interleukin-6 is the key acute-phase cytokine. Only a few studies concerned the association of interleukin-6 gene polymorphisms with febrile seizures.In this study, we aimed to investigate 3 cytokine singlenucleotide polymorphisms situated at positions –174 (G/C), –572 (G/C), and –597 (G/A) in the promoter region of the interleukin-6 gene for the first time in Egyptian children with febrile seizures. Febrile seizures are defined by the International League Against Epilepsy as “elevated or rapidly rising fever of short duration associated with uncomplicated seizure that does not predispose to epilepsy and is not accompanied by any neurologic abnormality, no previous neonatal seizures or a previous unprovoked seizure, and not meeting the criteria for other acute symptomatic seizures in children between 6 months and 5 years of age [2]. The main modulator of the condition is the seizure threshold, which varies strongly between individuals and is influenced by age, maturation, and genetic predisposition [5]
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