Interleukin (IL)-1?, IL-1?, and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy

Abstract

Proinflammatory cytokines, including interleukin (IL)‐1β, are known to modulate effects of neurotoxic neurotransmitters discharged during excitation or inflammation in the central nervous system (CNS). They also regulate development of glial scars at sites of CNS injury. To elucidate a genetic predisposition of temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS+), we studied polymorphisms in the IL‐1β, IL‐1α, and IL‐1 receptor antagonist (IL‐1RA) genes in 50 patients with TLE‐HS+ and in 112 controls. Fifty‐three patients who had TLE without HS were also examined (TLE‐HS−) as disease controls. The distribution of the biallelic polymorphism in the promoter region at position −511 of the IL‐1β gene (IL‐1B−511) was significantly different both between TLE‐HS+ patients and controls and between TLE‐HS+ and TLE‐HS− patients. The differences were due to overrepresentation of the homozygotes for IL‐1B−511∗︁2, which is suggested to be a high producer of IL‐1β, in TLE‐HS+ patients compared with both controls and TLE‐HS− patients. In contrast, there was no difference between TLE‐HS− patients and controls. Our data suggest that, in the homozygotes for IL‐1B−511∗︁2, minor events in development such as febrile convulsions could set up a cascade leading to HS. Ann Neurol 2000;47:571–574

Association study between interleukin 1β gene and epileptic disorders: a HuGe review and meta-analysis

“…Kanemoto et al 12 and Virta et al 9 were the first to report an association between the IL-1␤-511T polymorphism and TLEHS and FS, respectively. However, these findings were not replicated by others raising controversy about the real role of this genetic variant in the susceptibility to develop these diseases.…”

“…However, these findings have not been replicated by others 10,11 raising controversy about a role for this genetic variant in the susceptibility to develop these conditions. Conversely, the other two IL-1␤ promoter polymorphisms have not been associated with TLE 12,13 or FS. 14 Persistent difficulties in obtaining robust and replicable results in genetic association studies are almost certainly because genetic effects are small, requiring studies with many thousands of subjects to detect any effects.…”

Gene Expression in Temporal Lobe Epilepsy is Consistent with Increased Release of Glutamate by Astrocytes

“…Febrile seizures have been shown to be associated with increased IL-1β levels in CNS and blood plasma (68,69), and such IL-1β levels associated with a genetic polymorphism (70,71). IL-1β can act on the interleukin receptors on astrocytes and via the transcription factor NFκB induce a variety of molecules including the chemokines, cytokines and ERM proteins that are up-regulated in the sclerotic hippocampus.…”

Association of Interleukin-1β and Gene Polymorphisms with Liver Pathogenesis in Hepatitis B Virus Infection among Eastern Indian Population

“…21 Genotyping of IL-1b Promoter Polymorphisms and Detection of Penta-Allelic VNTR Polymorphism in Intron 2 of the IL-1RN gene Polymorphism at position À511 in the promoter region of IL-1b was detected by PCR-restriction fragment length polymorphism (PCR-RFLP) method. 22 By a single round PCR amplification, 304 b.p. long DNA fragment was amplified spanning the promoter region of IL-1b.…”