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Background: Dysfunction of gamma-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.

Purpose: To evaluate whether the inheritance of the apolipoprotein E (ApoE) epsilon4 allele is a risk factor for nonlesional temporal lobe epilepsy (TLE), and to determine whether the newly described -491 A/T ApoE polymorphism may independently affect the risk of nonlesional TLE., Methods: The study group consisted of 63 patients (35 women and 28 men; age at onset of epilepsy, 30.6 +/- 19.6 years; mean (+/-SD). All of them had received a diagnosis of nonlesional TLE after a detailed clinical, electroencephalographic, and brain magnetic resonance investigation. The ApoE polymorphisms were determined from blood samples by standard methods. The molecular study also was performed in 220 age- and sex-matched normal individuals., Results: There were no differences between TLE patients and controls in either allelic or genotypic frequencies of the ApoE and -491A/T polymorphisms. Moreover, no effect of ApoE or -491A/T polymorphisms was found on the age at onset and severity of epilepsy., Conclusions: The allelic and genotypic frequencies of ApoE polymorphisms in Italian patients with nonlesional TLE are comparable to control values, indicating that ApoE polymorphisms are not a significant genetic risk factor for the occurrence of nonlesional TLE.