An association between genotypic variations and protein expression of the glial glutamate transporter 2 in the human nucleus accumbens

Abstract

The glial glutamate transporter EAAT2 is responsible for the majority of synaptic glutamate clearance. Dysfunction of EAAT2 is strongly implicated in neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in the EAAT2 gene have been associated with an increased risk of pathological conditions that may result from changes in extracellular glutamate levels. Genetic variation in the metabotropic glutamate receptor 3 (GRM3) gene has been reported to affect EAAT2 mRNA. Therefore, the aim of this study was to investigate the association of EAAT2 (rs4755404 and rs1885343) and GRM3 (rs6465084) SNPs and EAAT2 protein expression in healthy subjects. Postmortem nucleus accumbens tissue from 37 normal subjects had EAAT2 protein determined and was genotyped for three SNPs. Expression of EAAT2 protein was observed in both monomeric (70kDa) and multimeric (150kDa) forms. A significantly lower expression of the monomer (P=0.037) was observed with the GG genotype than in A allele carriers of rs1885343. However, there were no differences in EAAT2 expression associated with genotypes or alleles of rs4755404 and rs6465084. This finding indicates an association between EAAT2 protein expression in the human nucleus accumbens and a genetic polymorphism of EAAT2.