IL-1[beta] associations with posttraumatic epilepsy development: A genetics and biomarker cohort study

• Published in: Epilepsia (Copenhagen) 2015-07, Vol.56 (7), p.991
• Main Authors: Diamond, Matthew L, Ritter, Anne C, Failla, Michelle D, Boles, Jennifer A, Conley, Yvette P, Kochanek, Patrick M, Wagner, Amy K
• Format: Article
• Language: English
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.13100

Summary Objective Posttraumatic epilepsy (PTE) is a significant complication following traumatic brain injury (TBI), yet the role of genetic variation in modulating PTE onset is unclear. We hypothesized that TBI-induced inflammation likely contributes to seizure development. We assessed whether genetic variation in the interleukin-1beta (IL-1[beta]) gene, Il-1[beta] levels in cerebral spinal fluid (CSF) and serum, and CSF/serum IL-1[beta] ratios would predict PTE development post-TBI. Methods We investigated PTE development in 256 Caucasian adults with moderate-to-severe TBI. IL-1[beta] tagging and functional single nucleotide polymorphisms (SNPs) were genotyped. Genetic variance and PTE development were assessed. Serum and CSF IL-1[beta] levels were collected from a subset of subjects (n = 59) during the first week postinjury and evaluated for their associations with IL-1[beta] gene variants, and also PTE. Temporally matched CSF/serum IL-1[beta] ratios were also generated to reflect the relative contribution of serum IL-1[beta] to CSF IL-1[beta]. Results Multivariate analysis showed that higher CSF/serum IL-1[beta] ratios were associated with increased risk for PTE over time (p = 0.008). Multivariate analysis for rs1143634 revealed an association between the CT genotype and increased PTE risk over time (p = 0.005). The CT genotype group also had lower serum IL-1[beta] levels (p = 0.014) and higher IL-1[beta] CSF/serum ratios (p = 0.093). Significance This is the first report implicating IL-1[beta] gene variability in PTE risk and linking (1) IL-1[beta] gene variation with serum IL-1[beta] levels observed after TBI and (2) IL-1[beta] ratios with PTE risk. Given these findings, we propose that genetic and IL-1[beta] ratio associations with PTE may be attributable to biologic variability with blood-brain barrier integrity during TBI recovery. These results provide a rationale for further studies (1) validating the impact of genetic variability on IL-1[beta] production after TBI, (2) assessing genetically mediated signaling mechanisms that contribute to IL-1[beta] CSF/serum associations with PTE, and (3) evaluating targeted IL-1[beta] therapies that reduce PTE. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. This article was previously published: IL-1[beta] associations with posttraumatic epilepsy development: A genetics and biomarker cohort study Vol. 55, Issue 7, 1109-1119, Article first publ