Abstract TP229: Impact Of Genetic Polymorphisms On The Risk Of Epilepsy Amongst Patients With Acute Brain Injury: A Systematic Review

Abstract

Introduction: Stroke and traumatic brain injury (TBI) accounts for 70% of secondary epilepsy in the adult population. The genetic architecture of epilepsy secondary to TBI or stroke is poorly understood. Objective: We undertook a systematic review to test the association of single nucleotide polymorphisms (SNPs) with the risk of posttraumatic epilepsy (PTE) and post-stroke epilepsy (PSE). Methods: We conducted a comprehensive literature search until 5 July 2022 in PubMed, Embase, PsycINFO, Web of Science, and Google Scholar. We preregistered the protocol of this systematic review on PROSPERO (CRD42022325617). We collated the association statistics from the articles to assess the association of SNPs with the risk of epilepsy amongst TBI or stroke patients. We assessed the study quality using the Quality of Genetic Association (Q-Genie) tool. We report Odds Ratio (OR) and Hazard Ratio (HR) with a 95% confidence interval (CI), including combined OR where a meta-analysis was possible. Results: The literature search yielded 420 articles, of which 16 were included in our systematic review. Q-Genie-based assessment of the literature found that 58% of the included studies were of poor quality. We examined published data on 127 SNPs from 32 genes identified in PTE and PSE patients. Twelve studies reported that 718 TBI patients (21%) suffered from PTE. Four studies reported PSE in 1192 stroke patients (50%). Eleven SNPs were associated with an increased risk of PTE. Three SNPs, TRMP6 rs2274924, ALDH2 rs671, CD40 -1C/T, were significantly associated with an increased risk of PSE, while two SNPs, AT1R rs12721273 and rs55707609, were significantly associated with reduced risk. Only two studies tested the association of APOE E4 with PTE; no other studies validated previously reported genetic association data. Hence, the limited data precluded meta-analysis of all but one SNP, i.e., the APOE E4 allele. The meta-analysis for the association of the APOE E4 allele with PTE was non-significant (OR 1.8, CI 0.6-5.6). Conclusions: The current evidence on the association of genetic polymorphisms in epilepsy secondary to TBI or stroke is of low quality and lacks validation. A collaborative effort to pool genetic data linked to epileptogenesis in stroke and TBI patients is warranted.