ArticleEpilepsia2016
Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure.
Article in Epilepsia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group.Brain imaging and behavior · 2021Pooled it
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- Myeloid cell genome-wide screen identifies variants associated with Mycobacterium tuberculosis-induced cytokine transcriptional responses.The Journal of clinical investigation · 2025Article
- Article
- New epilepsy therapies in development.Nature reviews. Drug discovery · 2024Review
- Neuropharmacological insight into preventive intervention in posttraumatic epilepsy based on regulating glutamate homeostasis.CNS neuroscience & therapeutics · 2023Review
- Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.Pharmacological reviews · 2022Review
- Review
- Genetic Variation and Impact on Outcome in Traumatic Brain Injury: an Overview of Recent Discoveries.Current neurology and neuroscience reports · 2021Review
- Paths to Successful Translation of New Therapies for Severe Traumatic Brain Injury in the Golden Age of Traumatic Brain Injury Research: A Pittsburgh Vision.Journal of neurotrauma · 2020Review
- Membrane transporters in traumatic brain injury: Pathological, pharmacotherapeutic, and developmental implications.Experimental neurology · 2019Review
- Neurotransmitter changes after traumatic brain injury: an update for new treatment strategies.Molecular psychiatry · 2019Review
- TBI Rehabilomics Research: Conceptualizing a humoral triad for designing effective rehabilitation interventions.Neuropharmacology · 2019Review
- Variability with Astroglial Glutamate Transport Genetics Is Associated with Increased Risk for Post-Traumatic Seizures.Journal of neurotrauma · 2019Article
- Altered glutamate clearance in ascorbate deficient mice increases seizure susceptibility and contributes to cognitive impairment in APP/PSEN1 mice.Neurobiology of aging · 2018Article
- Commonalities in epileptogenic processes from different acute brain insults: Do they translate?Epilepsia · 2018Review
- The pharmacogenomics of severe traumatic brain injury.Pharmacogenomics · 2017Review
- ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI.Neurocritical care · 2017Article
- Genetic Contributions to Acquired Epilepsies.Epilepsy currentsArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectivePosttraumatic seizures (PTS) commonly occur following severe traumatic brain injury (sTBI). Risk factors for PTS have been identified, but variability in who develops PTS remains. Excitotoxicity may influence epileptogenesis following sTBI. Glutamate transporters manage glutamate levels and excitatory neurotransmission, and they have been associated with both epilepsy and TBI. Therefore, we aimed to determine if genetic variation in neuronal glutamate transporter genes is associated with accelerated epileptogenesis and increased PTS risk after sTBI.
methodsIndividuals (N = 253) 18-75 years of age with sTBI were assessed for genetic relationships with PTS. Single nucleotide polymorphisms (SNPs) within SLC1A1 and SLC1A6 were assayed. Kaplan-Meier estimates and log-rank statistics were used to compare seizure rates from injury to 3 years postinjury for SNPs by genotype. Hazard ratios (HRs) were estimated using Cox proportional hazards regression for SNPs significant in Kaplan-Meier analyses adjusting for known PTS risk factors.
resultsThirty-two tagging SNPs were examined (SLC1A1: n = 28, SLC1A6: n = 4). Forty-nine subjects (19.37%) had PTS. Of these, 18 (36.7%) seized within 7 days, and 31 (63.3%) seized between 8 days and 3 years post-TBI. With correction for multiple comparisons, genotypes at SNP rs10974620 (SLC1A1) were significantly associated with time to first seizure across the full 3-year follow-up (seizure rates: 77.1% minor allele homozygotes, 24.8% heterozygotes, 16.6% major allele homozygotes; p = 0.001). When seizure follow-up began day 2 postinjury, genotypes at SNP rs7858819 (SLC1A1) were significantly associated with PTS risk (seizure rates: 52.7% minor allele homozygotes, 11.8% heterozygotes, 21.1% major allele homozygotes; p = 0.002). After adjusting for covariates, we found that rs10974620 remained significant (p = 0.017, minor allele versus major allele homozygotes HR 3.4, 95% confidence interval [CI] 1.3-9.3). rs7858819 also remained significant in adjusted models (p = 0.023, minor allele versus major allele homozygotes HR 3.4, 95%CI 1.1-10.5). SIGNIFICANCE: Variations within SLC1A1 are associated with risk of epileptogenesis following sTBI. Future studies need to confirm findings, but variation within neuronal glutamate transporter genes may represent a possible pharmaceutical target for PTS prevention and treatment.
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