1. GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy
- Author
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Mario Zappia, Pier Andrea Serra, Gioacchino Tedeschi, Emilio LePiane, Ida Manna, Antonio Gambardella, Angelo Labate, A. La Russa, Aldo Quattrone, Rita Cittadella, A. Di Costanzo, Rosanna Chifari, Umberto Aguglia, Simona Bonavita, Virginia Andreoli, Francesco Sasanelli, Gambardella, A, Manna, I, Labate, A, Chifari, R, LA RUSSA, A, Serra, P, Cittadella, R, Bonavita, Simona, Andreoli, V, Lepiane, E, Sasanelli, F, DI COSTANZO, A, Zappia, M, Tedeschi, Gioacchino, Aguglia, U, and Quattrone, A.
- Subjects
TLE ,Male ,medicine.medical_specialty ,Heterozygote ,Genotype ,receptors ,behavioral disciplines and activities ,Risk Assessment ,susceptibility ,Temporal lobe ,Central nervous system disease ,Epilepsy ,GABA ,Gene Frequency ,Polymorphism (computer science) ,Internal medicine ,medicine ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Receptor ,Polymorphism, Genetic ,A/G genotype ,Heterozygote advantage ,Middle Aged ,medicine.disease ,Endocrinology ,nervous system ,Epilepsy, Temporal Lobe ,Receptors, GABA-B ,Female ,Neurology (clinical) ,Age of onset ,Psychology ,psychological phenomena and processes - Abstract
Background: Dysfunction of γ-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE).Objective: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE.Methods: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 ± 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene.Results: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant.Conclusions: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.
- Published
- 2003