Variability with Astroglial Glutamate Transport Genetics Is Associated with Increased Risk for Post-Traumatic Seizures

Journal of Neurotrauma
Raj G KumarAmy K Wagner

Abstract

Excitotoxicity contributes to epileptogenesis after severe traumatic brain injury (sTBI). Demographic and clinical risk factors for post-traumatic seizures (PTS) have been identified, but genetic risk remains largely unknown. Thus, we investigated whether genetic variation in astroglial glutamate transporter genes is associated with accelerated epileptogenesis and PTS risk after sTBI. Adults (n = 267) 18-75 years old were assessed over a three-year period post-TBI. Single nucleotide polymorphisms (SNPs) throughout the SLC1A2 and SLC1A3 genes were assayed. Kaplan-Meier estimates and log-rank statistics were used to compare seizure frequencies by genotype. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HRs) for genotypes significant in Kaplan-Meier analyses. Thirty-nine tagging SNPs were examined (SLC1A2: n = 21, SLC1A3: n = 18). PTS developed in 57 (21.4%) individuals. Of those with PTS, n = 20 (35.7%) had an immediate/early seizure within the first seven days, and n = 36 (64.3%) had a late seizure occurring between eight days and three years post-TBI. When adjusting for multiple comparisons, rs4869682 genotypes (SLC1A3, GG vs. T-carriers) were associated with time to first seizure (p = 0.00...Continue Reading

References

Nov 1, 1996·The Journal of Biological Chemistry·O HaugetoN C Danbolt
Jan 15, 2000·Acta Neurochirurgica. Supplement·T YamamotoA Marmarou
May 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A C RimaniolD Dormont
Sep 5, 2001·The American Journal of Psychiatry·R E SmithJ H Meador-Woodruff
Mar 7, 2002·Epilepsia·E A LukyanetzP G Kostyuk
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Berkley A LynchBruno Fuks
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Oct 6, 2006·Journal of Neurotrauma·Frank K H van LandeghemAndreas von Deimling
Dec 17, 2008·Pharmacogenetics and Genomics·Slavé PetrovskiTerence J O'brien
Nov 27, 2010·Emergency Medicine Clinics of North America·Jennifer L MartindaleDaniel J Pallin
Nov 20, 2012·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Hadassa Goldberg-SternAviva Phatal-Valevski
May 28, 2013·Journal of Psychiatric Research·Adriana MedinaStanley J Watson
Jun 21, 2013·Frontiers in Cellular Neuroscience·Robert F HuntBret N Smith
Oct 29, 2013·Cellular and Molecular Life Sciences : CMLS·Massimiliano G BianchiOvidio Bussolati
Nov 22, 2013·The International Journal of Neuroscience·Gashirai K MbizvoAnthony G Marson
May 23, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Amy K WagnerJulie C Price
Jul 2, 2014·Seizure : the Journal of the British Epilepsy Association·Elisabeth HalmaMarian Majoie
Jul 25, 2014·Journal of Neurotrauma·Cynthia Harrison-FelixJuliet Haarbauer-Krupa
Oct 6, 2014·Epilepsy Research·Kanvel ShazadiGraeme J Sills
May 2, 2015·The Journal of Head Trauma Rehabilitation·Michelle D FaillaAmy K Wagner
Sep 13, 2015·Seizure : the Journal of the British Epilepsy Association·Alberto VerrottiGaetano Zaccara
Dec 17, 2015·Journal of Neurotrauma·Megan BrowningPatrick M Kochanek
Feb 15, 2016·Seizure : the Journal of the British Epilepsy Association·Hasan TekgülNihal Olgaç Dündar
Feb 19, 2016·Restorative Neurology and Neuroscience·Krista L CaudleFrank C Tortella
May 8, 2016·Neurorehabilitation and Neural Repair·John M MyrgaAmy K Wagner
Sep 23, 2016·Neurosurgery·Nancy CarneyJamshid Ghajar

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Citations

Sep 30, 2020·Epilepsy Currents·Piero Perucca, Ingrid E Scheffer
Jul 16, 2019·Neuroscience·Tássia Limana da SilveiraFelix Alexandre Antunes Soares
Sep 10, 2019·Neuropharmacology·Pavel Klein, Ivana Tyrlikova
Apr 23, 2020·Epilepsy & Behavior : E&B·Asla PitkänenNoora Puhakka
Mar 12, 2021·Current Neurology and Neuroscience Reports·Alwyn GomezFrederick A Zeiler
Oct 30, 2021·Zhurnal voprosy neĭrokhirurgii imeni N. N. Burdenko·K K KryukovaA A Potapov

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