Genetic variation of the human mu-opioid receptor and susceptibility to idiopathic absence epilepsy

Pharmacological and autoradiological studies suggest that mu-opioid recepto r (OPRM) mediated neurotransmission is involved in the generation of absenc e seizures. Mutation screening of the human OPRM gene identified a common a mino acid substitution polymorphism (Asn40Asp) that differentially modulate s the binding affinity of beta-endorphin and signal transduction of the rec eptor. The present association study tested the candidate gene hypothesis t hat the Asn40Asp substitution polymorphism in the N-terminal OPRM domain co nfers genetic susceptibility to idiopathic absence epilepsy (IAE). The geno types of the Asn40Asp polymorphism were assessed by allele-specific polymer ase chain reaction in 72 German IAE patients and in 340 ethnically matched control subjects. The frequency of the Asp40 allele was significantly incre ased in the IAE patients [f(Asp40) = 0.139] compared to the controls [f(Asp 40) = 0.078; chi(2) = 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 O PRM modulates neuronal excitability underlying the epileptogenesis of IAE. (C) 2000 Published by Elsevier Science B.V. All rights reserved.