Association of Glutamate Receptor Metabotropic 5 Gene (Grm5) Polymorphisms With Schizophrenia Susceptibility and Symptoms in a Chinese-Han Population

Abstract Objectives: Metabotropic glutamate receptor subtype 5 (mGluR5) is a potential target for the treatment of schizophrenia (SZ), with the evidence that mGluR5 modulates glutamatergic signaling through the NMDA receptor (NMDAR). Recently it was reported that the GRM5 gene (encoding mGluR5) is associated with SZ in the Scottish population. Methods: Here, case-control association analyses were performed in the Chinese-Han population to investigate if GRM5 gene is implicated in SZ. Twenty-four single nucleotide polymorphisms (SNPs) were analyzed in 528 paranoid SZ and 528 control subjects.Results: The genotypic and allelic frequencies of two SNPs, rs567990 and rs12421343 were significantly different between the case and control group (Genotype P = 0.007 and 0.011; Allele P = 0.003 and 0.021; respectively). The frequency of rs504183 allele was associated with SZ (P = 0.030). When subjects were stratified by gender, the rs12422021, rs567990, rs12421343, and rs7101540 remained significantly associated with SZ in female patients. Analysis of clinical features of SZ, as measured by the Positive and Negative Syndrome Scale (PANSS) inventory, displayed association of GRM5 to features of the general phenotype of SZ, including traits representing delusions, hallucinations and negative symptoms. Conclusion: In conclusion, our study provides further evidence that GRM5 is associated with SZ, and implies a putative sex difference for the effect of the gene.