A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia

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Introduction: Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamatereceptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of thehuman central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkageanalysis to contain a susceptibility locus for schizophrenia.Methods: We screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanesepatients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined theinfluence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfectedcells.Results: Twenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of asynonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patientswith schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activitybetween the T and C alleles.Conclusions: Our results support the possible association of a GRM7 gene polymorphism with genetic susceptibility toschizophrenia.