IL-1β associations with post-traumatic epilepsy: a genetic and biomarker cohort study

Diamond, Matthew (2014) IL-1β associations with post-traumatic epilepsy: a genetic and biomarker cohort study. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Objective: Post-traumatic 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 IL-1β gene, Il-1β levels in cerebral spinal fluid (CSF) and serum, and CSF/serum IL-1β ratios would predict PTE development post-TBI.

Methods: We investigated PTE development in 256 Caucasian adults with moderate to severe TBI. IL-1β tagging and functional single nucleotide polymorphisms (SNPs) were genotyped. Genetic variance and PTE development were assessed. Serum and CSF IL-1β levels were collected from a subset of subjects (n=59) during first week post injury and evaluated for their associations with IL-1β gene variants and also PTE. Temporally matched CSF/serum IL-1β ratios were also generated to reflect the relative contribution of serum IL-1β to CSF IL-1β.

Results: Multivariate analysis showed that higher CSF/serum IL-1β 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-1β levels (p=0.014) and higher IL-1β CSF/serum ratios (p=0.093).

Significance: This is the first report implicating IL-1β gene variability with PTE risk and linking 1) IL-1β gene variation with serum IL-1β levels observed after TBI and 2) IL-1β ratios with PTE risk. Given these findings, we propose that genetic and IL-1β ratio associations with PTE may be attributable to biological 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-1β production after TBI, 2) assessing genetically mediated signaling mechanisms that contribute to IL-1β CSF/serum associations with PTE, and 3) evaluating targeted IL-1β therapies that reduce PTE.

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Details

Item Type:	University of Pittsburgh ETD
Status:	Unpublished
Creators/Authors:	Creators Email Pitt Username ORCID Diamond, Matthew mld82@pitt.edu MLD82
ETD Committee:	Title Member Email Address Pitt Username ORCID Committee Chair Wagner, Amy wagnerak@upmc.edu AKW4 Committee Member Boison, Detlev dboison@downeurobiology.org Committee Member Conley, Yvette P. yconley@pitt.edu YCONLEY Committee Member Kochanek, Patrick M kochanekpm@ccm.upmc.edu Committee Member Van Cott, Anne Anne.VanCott@va.gov
Date:	22 April 2014
Date Type:	Publication
Defense Date:	5 February 2014
Approval Date:	22 April 2014
Submission Date:	11 March 2014
Access Restriction:	5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages:	47
Institution:	University of Pittsburgh
Schools and Programs:	David C. Frederick Honors College Dietrich School of Arts and Sciences > Neuroscience
Degree:	BPhil - Bachelor of Philosophy
Thesis Type:	Undergraduate Thesis
Refereed:	Yes
Uncontrolled Keywords:	Post-traumatic Epilepsy, Inflammation, TBI, genetic variation, IL-1β
Date Deposited:	22 Apr 2014 15:16
Last Modified:	22 Apr 2019 05:15
URI:	http://d-scholarship.pitt.edu/id/eprint/20713

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