title: Genetic variation of the human mu-opioid receptor and susceptibility to idiopathic absence epilepsy.
abstract: Pharmacological and autoradiological studies suggest that mu-opioid receptor (OPRM) mediated neurotransmission is involved in the generation of absence seizures. Mutation screening of the human OPRM gene identified a common amino acid substitution polymorphism (Asn40Asp) that differentially modulates the binding affinity of beta-endorphin and signal transduction of the receptor. The present association study tested the candidate gene hypothesis that the Asn40Asp substitution polymorphism in the N-terminal OPRM domain confers genetic susceptibility to idiopathic absence epilepsy (IAE). The genotypes of the Asn40Asp polymorphism were assessed by allele-specific polymerase chain reaction in 72 German IAE patients and in 340 ethnically matched control subjects. The frequency of the Asp40 allele was significantly increased in the IAE patients [f(Asp40) = 0.139] compared to the controls [f(Asp40) = 0.078; chi2 = 5.467, df = 1, P = 0.019; OR = 2.03; 95%-CI: 1.12-3.68]. This allelic association suggests that the functional Asp40 variant of OPRM modulates neuronal excitability underlying the epileptogenesis of IAE.
authors.affiliation: Department of Neurology, University Hospital Charité, Humboldt University of Berlin, Germany. sanderth@aol.com
authors.forename: T
authors.initials: T
authors.lastname: Sander
authors.forename: W
authors.initials: W
authors.lastname: Berlin
authors.forename: N
authors.initials: N
authors.lastname: Gscheidel
authors.forename: B
authors.initials: B
authors.lastname: Wendel
authors.forename: D
authors.initials: D
authors.lastname: Janz
authors.forename: M R
authors.initials: MR
authors.lastname: Hoehe
mesh_terms: D000483:Alleles; D004832:Epilepsy, Absence / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: D017450:Receptors, Opioid, mu