GAT-1 (rs2697153) and GAT-3 (rs2272400) polymorphisms are associated with febrile seizures and temporal lobe epilepsy.

The purpose of this study was to determine a possible association between two GABA transporter (GAT) single-nucleotide polymorphisms (SNPs), rs2697153 G>A in SLC6A1 (GAT-1) and rs2272400 C>T in SLC6A11 (GAT-3), and drug-resistant temporal lobe epilepsy (TLE). DNA was isolated from 138 TLE patients (from the neocortex) and 94 non-epileptic controls (from blood/buccal swaps), and amplified by polymerase chain reaction and subjected to restriction fragment length polymorphism assays. A subgroup of patients with a positive history of febrile seizures (FS+) and traumatic brain injury (TBI+) were investigated in a separate analysis. P values were obtained using the Chi-Square test and Fishers exact test. The GAT-1 SNP was different between patients and controls (p<0.05); the AA genotype was observed in 40% of the cases vs 23% of the controls (p<0.05). Thirty-one patients were FS+ and the GAT-3 CT genotype was observed significantly more frequently in the FS+ group (14%) than in the FS- group (1%; p<0.01). Thirteen patients were TBI+, and genotyping for GAT-1 and GAT-3 in these patients did not result in statistical differences between TBI+ and TBI- groups. The findings suggest that TLE is associated with GAT-1 and GAT-3 SNPs. More specifically, GAT-3 c1572T seems to be associated with TLE in patients with FS+. However, the pathophysiological consequences of these SNPs remain to be elucidated.