Association of metabotropic glutamate receptor 3 gene polymorphisms with schizophrenia risk: evidence from a meta-analysis

To date, the role of metabotropic glutamate receptor 3 (GRM3) rs274622, rs1468412, rs917071, rs6465084, and rs2299225 polymorphisms in schizophrenia remains controversial. To provide a clearer picture for the effect of the five most studied GRM3 polymorphisms on risk of schizophrenia, this meta-analysis with eligible data from published studies was performed. Relevant case–control studies were retrieved by literature search and selected according to established inclusion criteria. Odds ratios with 95% confidence intervals were used to assess the strength of association. A total of 33 individual studies were identified and included in our meta-analysis: nine for rs1468412, with 5,314 cases and 6,147 controls; six for rs917071, with 2,660 cases and 3,517 controls; seven for rs274622, with 3,820 cases and 4,015 controls; five for rs2299225, with 3,492 cases and 3,735 controls; and six for rs6465084, with 4,960 cases and 5,613 controls. However, no significant association was found between these GRM3 polymorphisms and schizophrenia in the overall population. With respect to rs1468412 polymorphism, a finding of very borderline statistical significance emerged in dominant comparison model for non-Asian populations, calling for large-scale verification to assess the marginally elevated risk of schizophrenia. In conclusion, these GRM3 polymorphisms have limited effect on the risks of schizophrenia. Further large and well-designed studies are needed to confirm this conclusion.