Lack of evidence of an allelic association of a functional GABRB3 exon 1a promoter polymorphism with idiopathic generalized epilepsy.
OBJECTIVE
Mutation screening and linkage disequilibrium mapping of the gene encoding the GABA(A) beta(3) subunit (GABRB3) identified a common genetic variant in the exon 1a promoter region (C-allele of rs4906902) which displayed a reduced transcriptional activity and showed a strong allelic association with childhood absence epilepsy (CAE). The present population-based association study tested whether the C-allele of rs4906902 confers susceptibility to CAE or other common syndromes of idiopathic generalized epilepsy (IGE) in a German sample.


METHODS
Seven hundred and eighty unrelated German IGE patients (250 CAE, 123 juvenile absence epilepsy, 303 juvenile myoclonic epilepsy (JME), 104 epilepsy with generalized tonic-clonic seizures on awakening) and 559 healthy population controls were genotyped for the single nucleotide polymorphism (SNP) rs4906902.


RESULTS
The frequency of the risk-conferring C-allele did not differ significantly between CAE patients (f(C)=0.190) and controls (f(C)=0.183; P=0.376, one-tailed). Similarly, no evidence for an allelic association was found for 373 patients with idiopathic absence epilepsy, 303 JME patients, and the entire IGE sample (P>0.77, two-tailed).


CONCLUSIONS
Our study failed to replicate an association of the common GABRB3 exon 1a promoter SNP rs4906902 with CAE. Moreover, the present results do not provide evidence that the common functional C-variant confers a substantial epileptogenic effect to a broad spectrum of IGE syndromes in the German population.
Hempelmann
Anne
A
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Street 10, 13125 Berlin, Germany.
Cobilanschi
Joana
J
Heils
Armin
A
Muhle
Hiltrud
H
Stephani
Ulrich
U
Weber
Yvonne
Y
Lerche
Holger
H
Sander
Thomas
T
D000483:Alleles; D004832:Epilepsy, Absence / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000235:genetics*
C546273:GABRB3 protein, human; D021122:Protein Subunits; D011963:Receptors, GABA-A