Interleukin-6 gene polymorphisms in Egyptian children with febrile seizures: a case–control study

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.

Analysis of plasma multiplex cytokines and increased level of IL-10 and IL-1Ra cytokines in febrile seizures

“…IL-6 is a cell signaling molecule that has been associated with many diseases, including inflammatory, neurological, vascular, and malignant processes [ 21 ]. The systemic concentration of IL-6 is mainly regulated at the level of expression, because IL-6 is rapidly cleared from the plasma and has a short plasma half-life of 20–60 min [ 22 ].…”

Cytokine levels in febrile seizure patients: A systematic review and meta-analysis

“…Their findings revealed that the patient group was more susceptible to FS. In addition, they reported a negative association between FSs and the C allele at the À174 position, indicating that this association could represent a protective effect against FSs [29].…”

“…The studies reported protein levels in serum or CSF and compared them with those of controls. We conducted meta-analyses of serum IL-1b levels based on five studies [10,19,23,25,28], CSF IL-1b based on two studies [10,28], serum TNF-a based on two studies [23,28] and serum IL-6 based on two studies [23,29]. The cytokine levels of patients and controls were expressed in pg/ml and significant difference was shown in P-value.…”

Neuroinflammatory mechanisms of post-traumatic epilepsy

“…Consistent with the notion that elevated IL-6 is associated with seizures in patients with ESES, immunomodulation that reduced IL-6 levels also improved electroencephalographic seizure activity [150]. IL-6 gene polymorphisms have also been implicated in pediatric epilepsy and febrile seizure cases [149,[151][152][153]. Transgenic mice that expressed elevated astrocytic IL-6 were more susceptible to NMDA-induced seizures and sub-threshold doses of kainic acid [154], with the latter causing mice to have severe tonic-clonic seizures and death.…”