The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study

Abstract

Objective:We aimed to explore the underlying pathomechanisms of the comorbidity between three common systemic autoimmune disorders (SADs) [i.e., insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA)] and temporal lobe epilepsy (TLE), using bioinformatics tools. We hypothesized that there are shared genetic variations among these four conditions. Methods: Different databases (DisGeNET, Harmonizome, and Enrichr) were searched to find TLE-associated genes with variants; their single nucleotide polymorphisms (SNPs) were gathered from the literature. We also did a separate literature search using PubMed with the following keywords for original articles: "TLE" or "Temporal lobe epilepsy" AND "genetic variation," "single nucleotide polymorphism," "SNP," or "genetic polymorphism." In the next step, the SNPs associated with TLE were searched in the LitVar database to find the shared gene variations with RA, SLE, and IDDM.Results: Ninety unique SNPs were identified to be associated with TLE. LitVar search identified two SNPs that were shared between TLE and all three SADs (i.e., IDDM, SLE, and RA). The first SNP was rs16944 on the Interleukin-1β (IL-1β) gene. The second genetic variation was ε4 variation of apolipoprotein E (APOE) gene.Significance: The shared genetic variations (i.e., rs16944 on the IL-1β gene and ε4 variation of the APOE gene) may explain the underlying pathomechanisms of the comorbidity between three common SADs (i.e., IDDM, SLE, and RA) and TLE. Exploring such shared genetic variations may help find targeted therapies for patients with TLE, especially those with drug-resistant seizures who also have comorbid SADs.

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study

“…Malekpour et al. ( 16 ) explored the relationship between frontal lobe epilepsy and three immune disorders, including RA, and showed that there were common genetic variants among the conditions. In addition, a meta-analysis emphasized that patients with RA have a higher risk of epilepsy than non-RA patients, and there was a negative correlation with age.…”