GAT-1 (rs2697153) and GAT-3 (rs2272400) polymorphisms are associated with febrile seizures and temporal lobe epilepsy. 2020

Olaf Emg Schijns, and Jeroen Bisschop, and Kim Rijkers, and Jim Dings, and Sabina Vanherle, and Patrick Lindsey, and Hubert Jm Smeets, and Govert Hoogland
Department of Neurosurgery, Maastricht University Medical Center, Maastricht,, Academic Center for Epileptology (ACE), Maastricht University Medical Center, Maastricht,, School of Mental Health and Neurosciences, Maastricht University, Maastricht.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D003294 Seizures, Febrile Seizures that occur during a febrile episode. It is a common condition, affecting 2-5% of children aged 3 months to five years. An autosomal dominant pattern of inheritance has been identified in some families. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy (i.e., a nonfebrile seizure disorder) following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. (From Menkes, Textbook of Child Neurology, 5th ed, p784) Convulsions, Febrile,Febrile Seizures,Pyrexial Seizure,Febrile Convulsion Seizure,Febrile Fit,Fever Convulsion,Fever Seizure,Pyrexial Convulsion,Seizure, Febrile, Complex,Seizure, Febrile, Simple,Convulsion, Febrile,Convulsion, Fever,Convulsion, Pyrexial,Convulsions, Fever,Convulsions, Pyrexial,Febrile Convulsion,Febrile Convulsion Seizures,Febrile Convulsions,Febrile Fits,Febrile Seizure,Fever Convulsions,Fever Seizures,Fit, Febrile,Fits, Febrile,Pyrexial Convulsions,Pyrexial Seizures,Seizure, Febrile,Seizure, Febrile Convulsion,Seizure, Fever,Seizure, Pyrexial,Seizures, Febrile Convulsion,Seizures, Fever,Seizures, Pyrexial
D004833 Epilepsy, Temporal Lobe A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the TEMPORAL LOBE, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic. (From Adams et al., Principles of Neurology, 6th ed, p321). Epilepsy, Benign Psychomotor, Childhood,Benign Psychomotor Epilepsy, Childhood,Childhood Benign Psychomotor Epilepsy,Epilepsy, Lateral Temporal,Epilepsy, Uncinate,Epilepsies, Lateral Temporal,Epilepsies, Temporal Lobe,Epilepsies, Uncinate,Lateral Temporal Epilepsies,Lateral Temporal Epilepsy,Temporal Lobe Epilepsies,Temporal Lobe Epilepsy,Uncinate Epilepsies,Uncinate Epilepsy
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D050485 GABA Plasma Membrane Transport Proteins A family of plasma membrane neurotransmitter transporter proteins that regulates extracellular levels of the inhibitory neurotransmitter GAMMA-AMINOBUTYRIC ACID. They differ from GABA RECEPTORS, which signal cellular responses to GAMMA-AMINOBUTYRIC ACID. They control GABA reuptake into PRESYNAPTIC TERMINALS in the CENTRAL NERVOUS SYSTEM through high-affinity sodium-dependent transport. GABA Transporter,Neurotransmitter Transport Proteins, GABA-Specific,Neurotransmitter Transporters, GABA-Specific,GABA Plasma Membrane Transporter Proteins,GABA Transporter 1,GABA Transporter 2,GABA Transporter 3,GABA Transporter 4,GABA Transporters,GAT-1 Transporter,GAT-2 Transporter,GAT-3 Transporter,GAT-4 Transporter,GAT1 Transporter,GAT2 Transporter,GAT3 Transporter,Gamma-Aminobutyric Acid Plasma Membrane Transport Proteins,GABA-Specific Neurotransmitter Transporters,GAT 1 Transporter,GAT 2 Transporter,GAT 3 Transporter,GAT 4 Transporter,Gamma Aminobutyric Acid Plasma Membrane Transport Proteins,Neurotransmitter Transport Proteins, GABA Specific,Neurotransmitter Transporters, GABA Specific,Transporter 2, GABA,Transporter, GABA,Transporter, GAT-2,Transporter, GAT-4,Transporter, GAT2,Transporters, GABA,Transporters, GABA-Specific Neurotransmitter
D020641 Polymorphism, Single Nucleotide A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population. SNPs,Single Nucleotide Polymorphism,Nucleotide Polymorphism, Single,Nucleotide Polymorphisms, Single,Polymorphisms, Single Nucleotide,Single Nucleotide Polymorphisms

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