GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy
A Gambardella1, I Manna, A Labate
1Institute of Neurology, School of Medicine, Catanzaro, Italy.
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.
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