title: Failure to replicate an allelic association between an exon 8 polymorphism of the human alpha(1A) calcium channel gene and common syndromes of idiopathic generalized epilepsy.
abstract: The present replication study tested the validity of a previously reported allelic association between a single nucleotide polymorphism in exon 8 (SNP8) of the gene encoding the alpha(1A)-calcium channel subunit (CACNA1A) and common subtypes of idiopathic generalized epilepsy (IGE). Pyrosequencing was applied to assess the SNP8 genotypes in 354 unrelated German IGE probands, both parents of 118 IGE probands, and 186 healthy control subjects of German descent. Our population-based association analysis did not provide evidence for an allelic association of SNP8 with either IGE or two phenotypically more homogeneous IGE subtypes, consisting of either 139 probands with juvenile myoclonic epilepsy or 207 probands whose IGE started with typical absence seizures (P>0.72). In addition, the transmission disequilibrium test did not indicate a preferential transmission of SNP8 alleles in 97 informative parent-child transmissions (McNemar chi(2)=0.093, df=1, P=0.76). Accordingly, we failed to confirm previous evidence that genetic variation of the CACNA1A gene confers susceptibility to common IGE syndromes.
authors.affiliation: Epilepsy Genetics Group, Department of Neurology, University Clinic Charité, Humboldt University of Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. sanderth@aol.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Toliat
authors.forename: Armin
authors.initials: A
authors.lastname: Heils
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
mesh_terms: D000483:Alleles; D015220:Calcium Channels / Q000235:genetics*; D004261:DNA Replication; D004829:Epilepsy, Generalized / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D021122:Protein Subunits
chemical_list: D015220:Calcium Channels; D021122:Protein Subunits