Genetic biomarkers of posttraumatic epilepsy: A systematic review

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.

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.

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).

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.