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Year, Volume, Issue, Page(s):

, 57, 6, 984-993

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Study investigated whether genetic variation in neuronal glutamate transporter genes is associated with accelerated epileptogenesis and increased risk of posttraumatic seizures (PTS) after severe traumatic brain injury (sTBI). A total of 253 individuals with sTBI 18-75 years of age 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 post injury for SNPs by genotype. Hazard ratios were estimated using Cox proportional hazards regression for SNPs significant in Kaplan-Meier analyses adjusting for known PTS risk factors. Thirty-two tagging SNPs were examined. Forty-nine subjects (19.37 percent) had PTS. Of these, 18 (36.7 percent) seized within 7 days, and 31 (63.3 percent) 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. When seizure follow-up began day 2 post injury, genotypes at SNP rs7858819 (SLC1A1) were significantly associated with PTS risk. After adjusting for covariates, rs10974620 remained significant; rs7858819 also remained significant in adjusted models. Findings indicate that 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.


Ritter, Anne C., Kammerer, Candace M., Brooks, Maria M., Conley, Yvette P., Wagner, Amy K.