GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy
Journal - Neurology
Background: Dysfunction of -aminobutyric acid (GABA) (B) receptorshas been implicated in the pathogenesis of temporal lobe epilepsy(TLE).Objective: To evaluate the genetic contribution of cloned humanGABA(B) receptors to TLE.Methods: The authors genotyped 141 patients (78 women and 63men; mean age = 49.1 ± 18.0 years) with nonlesional TLEand 372 age- and sex-matched normal individuals for the knownpolymorphism G1465A in the human GABA(B) receptor 1 [GABA(B)]gene.Results: There was a highly significant overrepresentation ofthe G1465A heterozygote in patients with TLE compared with controls.The A/G genotype was found in 17% of the 141 patients with TLEand in only 0.5% of the 372 controls (p < 0.0001). The authorsalso found that patients carrying the A allele had a significantlyhigher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) ofdeveloping drug-resistant TLE. Furthermore, the age at onsetof 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)polymorphism (G1465A) confers a highly increased susceptibilityto TLE. Moreover, it seems to influence the severity of thiscommon epileptic disorder.