Lack of evidence of an allelic association of a functional GABRB3 exon 1a promoter polymorphism with idiopathic generalized epilepsy

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• 作者：Anne Hempelmann ; Joana Cobilanschi ; Armin Heils ; Hiltrud Muhle ; Ulrich Stephani ; Yvonne Weber ; Holger Lerche ; Thomas S ; er
• 关键词：Childhood absence epilepsy ; Idiopathic generalized epilepsy ; GABRB3 ; Association ; Genetics
• 刊名：Epilepsy Research
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：74
• 期：1
• 页码：28-32
• 全文大小：160 K

文摘

Summary

Purpose

Mutation screening and linkage disequilibrium mapping of the gene encoding the GABA_A β₃ 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).

Conclusion

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.