title: Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy.
abstract: OBJECTIVE
  Quantitative trait loci (QTL) mapping in mice revealed a seizure-related QTL (Szs1), for which the inward-rectifying potassium channel Kcnj10 is the most compelling candidate gene. Association analysis of the human KCNJ10 gene identified a common KCNJ10 missense variation (Arg271Cys) that influences susceptibility to focal and generalized epilepsies. The present replication study tested the initial finding that the KCNJ10 Cys271 allele is associated with seizure resistance to common syndromes of idiopathic generalized epilepsy (IGE).
  
  
  METHODS
  The study sample comprised 563 German IGE patients and 660 healthy population controls. To search for seizure type-specific effects, two IGE subgroups were formed, comprising 258 IGE patients with typical absences (IAE group) and 218 patients with juvenile myoclonic epilepsy (JME group). A TaqMan nuclease assay was used to genotype the KCNJ10 single nucleotide polymorphism c.1037C > T (dbSNP: rs1130183) that alters amino acid at position 271 from arginine to cysteine.
  
  
  RESULTS
  Replication analysis revealed a significant decrease of the Cys271 allele frequency in 446 IGE patients compared to controls (chi2 = 3.52, d.f. = 1, P = 0.030, one-sided; OR(Cys271+) = 0.69; 95% CI: 0.50-0.95). Among the IGE subgroups, lack of the Cys271 allele was accentuated in the JME group (chi2 = 5.20, d.f. = 1, P = 0.011, one-sided).
  
  
  CONCLUSIONS
  Our results support previous evidence that the common KCNJ10 Arg271Cys missense variation influences seizure susceptibility of common IGE syndromes.
authors.affiliation: Gene Mapping Center, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Lenzen
authors.forename: A
authors.initials: A
authors.lastname: Heils
authors.forename: S
authors.initials: S
authors.lastname: Lorenz
authors.forename: A
authors.initials: A
authors.lastname: Hempelmann
authors.forename: S
authors.initials: S
authors.lastname: Höfels
authors.forename: F W
authors.initials: FW
authors.lastname: Lohoff
authors.forename: B
authors.initials: B
authors.lastname: Schmitz
authors.forename: T
authors.initials: T
authors.lastname: Sander
mesh_terms: D000483:Alleles; D001120:Arginine / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D000098854:Kcnj10 Channel
chemical_list: D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D001120:Arginine; D003545:Cysteine