Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes.
Several potassium channel genes have been implicated in epilepsy. We have investigated three such genes, KCNJ3, KCNJ6 and KCNQ2, by association studies using a broad sample of idiopathic generalised epilepsy (IGE) unselected by syndrome. One of the two single nucleotide polymorphisms (SNPs) examined in one of the inward rectifying potassium channel genes, KCNJ3, was associated with IGE by genotype (P=0.0097), while its association by allele was of borderline significance (P=0.051). Analysis of the different clinical subgroups within the IGE sample showed more significant association with the presence of absence seizures (P=0.0041) and which is still significant after correction for multiple testing. Neither SNP in the other rectifying potassium channel gene, KCNJ6, was associated with IGE or any subgroup. None of the three SNPs in the voltage-gated potassium channel gene, KCNQ2, was associated with IGE. However, one SNP was associated with epilepsy with generalised tonic clonic seizures only (P=0.016), as was an SNP approximately 56 kb distant in the closely linked nicotinic acetylcholine gene CHRNA4 (P=0.014). These two SNPs were not in linkage disequilibrium with each other, suggesting that if they are not true associations they have independently occurred by chance. Neither association remains significant after correcting for multiple testing.
Chioza
B
B
Department of Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, UK.
Osei-Lah
A
A
Wilkie
H
H
Nashef
L
L
McCormick
D
D
Asherson
P
P
Makoff
A J
AJ
D020413:3' Untranslated Regions; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002890:Chromosomes, Human, Pair 20; D017931:DNA Primers; D004829:Epilepsy, Generalized / Q000209:etiology / Q000235:genetics*; D005091:Exons; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D051658:KCNQ2 Potassium Channel; D015810:Linkage Disequilibrium / Q000235:genetics; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D044465:White People / Q000235:genetics
D020413:3' Untranslated Regions; D017931:DNA Primers; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated