Is variation in the GABA(B) receptor 1 gene associated with temporal lobe epilepsy ?

Abstract

<h4>Purpose</h4>gamma-Aminobutyric acid (GABA)-receptor genes are prime candidates for a role in seizure susceptibility. An association between the c.1465G-->A variant in the GABA(B) receptor 1 gene (GABBR1) and susceptibility to temporal lobe epilepsy (TLE) has been reported in an Italian cohort. We sought to replicate this association in an independent Australian cohort.<h4>Methods</h4>The 234 patients with TLE and 164 healthy controls were genotyped for the c.1465G-->A variant, by using inclusion criteria identical to those of the first study.<h4>Results</h4>The c.1465G-->A variant was found in one TLE patient and one control subject. Genotype and allele frequencies did not differ between groups.<h4>Conclusions</h4>We did not replicate the reported associations between the c.1465G-->A variant and susceptibility to TLE. We suggest that the initial positive association may be due to undetected population stratification; the importance of genomic control is emphasized. Population-specific effects also may play a role, and we highlight the need to demonstrate an in vitro functional effect to give biologic meaning to any proposed association.