ALLELIC ASSOCIATION OF JUVENILE ABSENCE EPILEPSY WITH A GLUR5 KAINATERECEPTOR GENE (GRIK1) POLYMORPHISM

Juvenile absence epilepsy (JAE) is a common subtype of idiopathic gene ralized epilepsy (IGE), Hereditary factors play a major role in its et iology, The important function of glutamate receptors (GluRs) in excit atory neurotransmission, synaptic plasticity, and neurodevelopment sug gests their involvement in epileptogenesis. A tetranucleotide repeat p olymorphism in the non-coding region of the kainate-selective GluR5 re ceptor gene (GRIK1) on chromosome 21q22.1 provides the tool to investi gate this candidate gene, The present association and linkage study te sted the hypothesis that allelic variants of GRIK1 confer genetic susc eptibility to the pathogenesis of JAE, Our family-based association an alysis using the haplotype-based haplotype relative risk statistic rev ealed an association of JAE, with the nine-repeat containing allele of the GRIK1 tetranucleotide polymorphism (chi(2) = 8.31, df = 1, P = 0. 004), Supportive evidence for linkage to a JAE related IGE spectrum (Z (max) = 1.67 at GRIK1) under an autosomal dominant mode of inheritance and significant allele sharing (P < 0.05) among the affected family m embers suggest that allelic variants of GRIK1 contribute a major genet ic determinant to the pathogenesis of JAE-related phenotypes. (C) 1997 Wiley-Liss, Inc.