Association analysis of the Arg220His variation of the human gene encoding the GABA delta subunit with idiopathic generalized epilepsy.
OBJECTIVE
Mutation analysis of the gene encoding the GABA delta subunit (GABRD) identified a common missense variation (c.659G>A; Arg220His) of which the His220 allele displayed decreased GABA(A) alpha(1)beta(2)delta 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).


CONCLUSIONS
Our results provide no evidence that the functional GABRD His220 allele mediates a substantial susceptibility effect to common IGE syndromes in the German population.
Lenzen
Kirsten P
KP
Gene Mapping Center, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Heils
Armin
A
Lorenz
Susanne
S
Hempelmann
Anne
A
Sander
Thomas
T
D001120:Arginine / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011963:Receptors, GABA-A / Q000235:genetics*; D012189:Retrospective Studies
C464500:GABRD protein, human; D011963:Receptors, GABA-A; D006639:Histidine; D001120:Arginine