Devyn Cotter1, Andrew Kelso2, Aidan Neligan3. 1. Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. 2. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. 3. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: a.neligan@ucl.ac.uk.
Abstract
INTRODUCTION: Posttraumatic epilepsy (PTE) is caused by traumatic brain injury (TBI) and is an important contributor to the overall social and economic burden of epilepsy. Epidemiological studies suggest that there is a genetic contribution to the development of PTE. Identification of clinically useful genetic biomarkers is important for advancements in diagnosis and treatment of PTE. METHODS: A systematic review was performed on the existing literature of genetic biomarkers of posttraumatic epilepsy (PTE). A multi-database search yielded 4 articles deemed suitable for review. Potential genetic biomarkers were identified and critically evaluated. RESULTS & DISCUSSION: Biomarkers identified included single nucleotide polymorphism (SNP) rs1143634 of the interkeukin-1β (IL-1β) gene, SNPs rs3828275, rs3791878, and rs769391 of the glutamic acid decarboxylase 1 (GAD1) gene, SNPs rs3766553 and rs10920573 of the adenosine A1 receptor (A1AR) gene, and the functional variant C677T of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The most promising biomarkers identified were IL-1β rs1143634 and A1AR rs10920573. Both had heterogenous at risk genotypes (CT). Those with IL-1β rs1143634 CT genotype developed PTE in 47.7% of cases (p=0.008) and those with A1AR rs10920573 CT genotype developed PTE in 19.2% of cases (p=0.022). CONCLUSION: The majority of articles were preliminary with a need for validation of results. There is a need for continued high calibre research in order to validate the currently identified genetic biomarkers as well as to discover new genetic biomarkers in PTE.
INTRODUCTION:Posttraumatic epilepsy (PTE) is caused by traumatic brain injury (TBI) and is an important contributor to the overall social and economic burden of epilepsy. Epidemiological studies suggest that there is a genetic contribution to the development of PTE. Identification of clinically useful genetic biomarkers is important for advancements in diagnosis and treatment of PTE. METHODS: A systematic review was performed on the existing literature of genetic biomarkers of posttraumatic epilepsy (PTE). A multi-database search yielded 4 articles deemed suitable for review. Potential genetic biomarkers were identified and critically evaluated. RESULTS & DISCUSSION: Biomarkers identified included single nucleotide polymorphism (SNP) rs1143634 of the interkeukin-1β (IL-1β) gene, SNPs rs3828275, rs3791878, and rs769391 of the glutamic acid decarboxylase 1 (GAD1) gene, SNPs rs3766553 and rs10920573 of the adenosine A1 receptor (A1AR) gene, and the functional variant C677T of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The most promising biomarkers identified were IL-1β rs1143634 and A1AR rs10920573. Both had heterogenous at risk genotypes (CT). Those with IL-1β rs1143634 CT genotype developed PTE in 47.7% of cases (p=0.008) and those with A1AR rs10920573 CT genotype developed PTE in 19.2% of cases (p=0.022). CONCLUSION: The majority of articles were preliminary with a need for validation of results. There is a need for continued high calibre research in order to validate the currently identified genetic biomarkers as well as to discover new genetic biomarkers in PTE.
Authors: Brad G Kurowski; Amery Treble-Barna; Valentina Pilipenko; Shari L Wade; Keith Owen Yeates; H Gerry Taylor; Lisa J Martin; Anil G Jegga Journal: Front Genet Date: 2019-05-22 Impact factor: 4.599
Authors: Frederick A Zeiler; Charles McFadyen; Virginia F J Newcombe; Anneliese Synnot; Emma L Donoghue; Samuli Ripatti; Ewout W Steyerberg; Russel L Gruen; Thomas W McAllister; Jonathan Rosand; Aarno Palotie; Andrew I R Maas; David K Menon Journal: J Neurotrauma Date: 2019-06-07 Impact factor: 5.269