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


METHODS
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.


RESULTS
The c.1465G-->A variant was found in one TLE patient and one control subject. Genotype and allele frequencies did not differ between groups.


CONCLUSIONS
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.
Tan
Nigel C K
NC
Epilepsy Research Centre and Department of Medicine (Neurology), University of Melbourne, Australia.
Heron
Sarah E
SE
Scheffer
Ingrid E
IE
Berkovic
Samuel F
SF
Mulley
John C
JC
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001315:Australia / Q000453:epidemiology; D015331:Cohort Studies; D003431:Cross-Cultural Comparison; D004833:Epilepsy, Temporal Lobe / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D018080:Receptors, GABA-B / Q000235:genetics*; D015203:Reproducibility of Results; D044465:White People / Q000235:genetics
D005819:Genetic Markers; D018080:Receptors, GABA-B