Related Experiment Videos
Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia
1Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, 305-8575, Ibaraki, Japan.
Abstract:
NMDA receptor dysfunction may be involved in the pathophysiology of schizophrenia. Based on this hypothesis, we screened 48 Japanese patients with schizophrenia for mutations in the coding region of the NMDAR2B subunit gene (GRIN2B). An association study between the identified DNA sequence variants and schizophrenia was performed in 268 Japanese patients with schizophrenia and 337 Japanese control subjects. Eight single nucleotide polymorphisms were detected, all of which were synonymous. The association sample showed statistically significant excesses of homozygosity for the polymorphisms in the 3' region of the last exon in the patients with schizophrenia (P = 0.004) and higher frequency of the G allele of the 366C/G polymorphism (corrected P = 0.04) in the patients than in the controls. Although we did not detect NMDAR2B protein variants, our findings support the possibility that the GRIN2B gene or a locus in linkage disequilibrium with it may confer susceptibility to schizophrenia. Replication studies in independent samples are warranted.
Insights
This study investigated the GRIN2B gene in schizophrenia, finding specific DNA sequence variants associated with the disorder. These findings suggest GRIN2B may play a role in schizophrenia susceptibility.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- NMDA receptor dysfunction is a potential factor in schizophrenia pathophysiology.
- The NMDAR2B subunit gene (GRIN2B) is a candidate gene for schizophrenia susceptibility.
Purpose of the Study:
- To screen for mutations in the GRIN2B gene in Japanese schizophrenia patients.
- To investigate the association between GRIN2B DNA sequence variants and schizophrenia.
Main Methods:
- Screening of the GRIN2B coding region in 48 Japanese schizophrenia patients.
- Association study of identified variants in 268 patients and 337 controls.
- Analysis of single nucleotide polymorphisms (SNPs) and allele frequencies.
Main Results:
- Eight synonymous single nucleotide polymorphisms (SNPs) were detected in the GRIN2B gene.
- A significant excess of homozygosity for 3' region polymorphisms was observed in patients (P = 0.004).
- Higher frequency of the G allele for the 366C/G polymorphism was found in patients (corrected P = 0.04).
Conclusions:
- While no NMDAR2B protein variants were found, the study supports GRIN2B's potential role in schizophrenia susceptibility.
- The findings suggest GRIN2B or a linked locus may confer risk for schizophrenia.
- Further replication studies are recommended to validate these genetic associations.