Association analysis of the Arg220His variation of the human gene encoding the GABA δ subunit with idiopathic generalized epilepsy

Purpose: Mutation analysis of the gene encoding the GABA δ subunit ( GABRD ) identified a common missense variation (c.659G>A; Arg220His) of which the His220 allele displayed decreased GABA A α 1 β 2 δ receptor current amplitudes. The present association study tested whether the functional GABRD His220 allele confers susceptibility to common syndromes of idiopathic generalized epilepsy (IGE). Methods: Five hundred and sixty two unrelated German IGE patients and 664 healthy population controls were genotyped for the c.659G>A polymorphism in exon 6 of the GABRD gene. Results: His220 allele frequencies did not differ significantly between IGE patients (2.3%) and the controls (2.8%; P =0.46). Likewise, no evidence for an allelic association was found with juvenile myoclonic epilepsy ( n =218; 2.8%; P =0.97) or idiopathic absence epilepsy ( n =260; 2.3%; P =0.56). Conclusion: Our results provide no evidence that the functional GABRD His220 allele mediates a substantial susceptibility effect to common IGE syndromes in the German population.