Assessment of the relationship between generalized convulsive epilepsy and systemic inflammatory regulators: a bidirectional Mendelian randomization study

Background Generalized convulsive epilepsy (GCE), an important subtype of epilepsy, is a syndrome neuronal dysfunction characterized by diffuse abnormal discharge neurons within the brain. Compounding evidence suggests correlation between and inflammatory factors, for instance, cyclooxygenase-2, interleukin-1β, interleukin-6. Elevated levels factors have been observed in patients with several animal models. Therefore, inflammation may be closely associated pathogenesis progression GCE. However, cause-and-effect relationship two difficult to determine because small sample sizes confounding factors. Methods To test causality 41 cytokines on GCE, we conducted two-sample Mendelian randomization (MR) based largest latest genome-wide association study (GWAS) involving 290 cases 453,521 European controls GWAS meta-analysis consisting from 8,293 individuals. Results R confirmed bidirectional causal link Genetically predicted increased hepatocyte growth factor decreased eotaxin interleukin-18 are risk GCE (OR = 1.904, 95% CI 1.019–3.561, p 0.044; OR 0.641, 0.417–0.984, 0.042; 0.482, 0.251–0.927, 0.046). Furthermore, presence related increase multiple cytokines, such as macrophage protein-1α, interleukin-12p70, interleukin-17, interleukin-1 receptor antagonist, basic fibroblast 1.038, 1.005–1.073, 0.024; 1.031, 1.009–1.054, 0.006; 1.027, 1.002–1.053, 0.037; 1.037, 1.003–1.072, 0.032; 1.032, 1.000–1.066, 0.048; 1.025, 1.003–1.048, 0026). Conclusion A existed Detecting significantly altered concentrations great significance screening predicting their occurrence. Moreover, available pharmacological treatments focused primarily suppressing seizures. In future, altering concentration these body through targeted anti-inflammatory therapy modify epileptogenic mechanism prevent recurrence refractoriness become key new treatments.