N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) G1001C polymorphism and susceptibility to schizophrenia: A meta-analysis

A comprehensive literature search was conducted to identify all case-control studies investigating the association between GRIN1 G1001C polymorphism and schizophrenia susceptibility (MIM: 138249; dbSNP: rs 11146020). A total of 6 eligible studies (including 1639 schizophrenia cases and 1489 controls) were identified for the meta-analysis. Including all studies, there was significant heterogeneity between studies. In overall the GC (OR=1.00, 95 % CI: 0.0.85-1.19) and CC (OR=1.09, 95 % CI: 0.67-1.79) genotypes were not associated with schizophrenia risk compared with the GG genotype. In one study patients were diagnosed using DSM-IIIR criteria and in another study the genotypic frequencies of control subjects showed significant deviation from the expected frequencies according to the Hardy-Weinberg equilibrium. After excluding these studies from the meta-analysis, the heterogeneity between studies dramatically decreased. Statistical analysis showed that the GC genotype compared with the GG genotype significantly increased the risk of schizophrenia (OR=1.85, 95 % CI: 1.43-2.42, P<0.0001). The CC versus GG genotype significantly increased the schizophrenia risk (OR=2.46, 95% CI: 1.17-6.84, P=0.017). There was significant linear trend for presence of 0, 1, and 2 of the C allele and risk of schizophrenia (χ(2)=25.45, P<0.0001). In conclusion, the C variant allele may be associated with an increased risk for developing schizophrenia.