Genetic susceptibility to febrile seizures: Case-control association studies

Objective: A genetic predisposition to febrile seizures (FS) has long been recognized. The inheritance appears to be polygenic in small families or sporadic cases of FS encountered in daily clinical practice. To determine whether candidate genes are responsible for the susceptibility to FS, we have performed genetic association studies in FS patients and controls. Methods: The single-nucleotide polymorphisms (SNPs) of genes involved in immune response (interleukin (IL) 1B), endocannabinoid signaling (CNR1), acid–base balance (SLC4A3, SLC9A1, SLC9A3), gap junction channel (CX43), and GABAA receptor trafficking (PRIP1) were examined in 249 FS patients (186 simple and 63 complex FS) and 225 controls. Results: There were no significant differences in the allele frequencies of the SNPs between controls and all FS, simple FS, and complex FS patients. When the simple FS patients were divided into two groups according to either having (familial) or not having a family history of FS in close relatives (sporadic), there was a significant association between IL1B −511 SNP and sporadic simple FS (p = 0.003). Conclusions: These data suggest that cytokine genes may act as enhancers or attenuators of FS susceptibility. Genetic association study may be an effective approach to understanding the molecular basis of FS at least in a subgroup of patients.