Abstract
BackgroundSchizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. Abnormal glutamate ionotropic N-methyl-D-aspartate receptor (NMDA) type subunit 1 (NR1) may be a potential cause of schizophrenia.MethodsWe conducted a case-control study to investigate the association between the GRIN1 gene, which encodes the NR1 subunit, and the risk of schizophrenia in a northern Chinese Han population using Sanger DNA sequencing. The dual luciferase reporter assay was used to detect the influence of two different haplotypes on GRIN1 gene expression.ResultsSeven SNPs (single nucleotide polymorphisms), including rs112421622 (− 2019 T/C), rs138961287 (− 1962--1961insT), rs117783907 (−1945G/T), rs181682830 (−1934G/A), rs7032504 (-1742C/T), rs144123109 (−1140G/A), and rs11146020 (−855G/C) were detected in the study population. Rs117783907 (−1945G/T) was associated with the occurrence of schizophrenia as a protective factor. The genotype frequencies of rs138961287 (− 1962--1961insT) and rs11146020 (−855G/C) were statistically different between cases and controls (p < 0.0083). The other four variations were not shown to be associated with the disease. Two haplotypes were composed of the seven SNPs, and distribution of T-del-G-G-C-G-G was significantly different between the case and control groups. However, the dual luciferase reporter assay showed that neither of the haplotypes affected luciferase expression in HEK-293 and SK-N-SH cell lines.ConclusionsThe GRIN1 gene may be related to the occurrence of schizophrenia. Additional research will be needed to fully ascertain the role of GRIN1 in the etiology of schizophrenia.
Highlights
Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology
(− 1962--1961insT), rs117783907 (−1945G/T) and rs111 46020 (−855G/C) are related to schizophrenia. Another association study in a northern Chinese Han population reported that the C allele frequency of rs11146020 reduced the risk of schizophrenia [19], this allele was reported to be associated with schizophrenia as a risk factor in an Italian population [20]
Using Sanger DNA sequencing, we illustrated that rs11146020, rs138961287, and rs117783907 in the promoter region of the GRIN1 gene are associated with schizophrenia in a northern Chinese Han population
Summary
Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. Abnormal glutamate ionotropic N-methyl-D-aspartate receptor (NMDA) type subunit 1 (NR1) may be a potential cause of schizophrenia. Of the various glutamate receptors, NMDA receptors have received more attention due to their pivotal role in axonal formation, long-term potentiation, and excitotoxicity [3, 4]. Phenylcyclohexyl piperidine (PCP), which blocks a NMDA glutamate receptor subtype [7], induces a psychotomimetic state that closely resembles schizophrenia [8]. These findings imply that NMDA receptor dysfunction might be involved in the etiology of the CNS disorders [9]
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