ABSTRACT
A well established model for the pathophysiology of schizophrenia postulates a role for the NMDA-mediated glutamate transmission. The human gene coding for the 2B subunit of the NMDA receptor (GRIN2B) is considered a candidate based on its selective expression in brain. To evaluate the hypothesis that GRIN2B acts as a major gene in determining susceptibility to schizophrenia, a case-control association study was performed. Five single nucleotide polymorphisms (SNPs) were genotyped in 188 Italian patients and 156 control subjects. The association study showed a marginally significant excess of homozygosity for the polymorphism located in the 3'UTR region (P = 0.04). No other difference in genotype and allele frequencies was found in schizophrenics as compared to the control series. The case-control study was also carried out on estimated haplotypes, confirming a trend for association (P = 0.04). These results suggest that GRIN2B variations might be linked with susceptibility to schizophrenia. Replication studies on larger samples are warranted to further test this hypothesis.
Subject(s)
Polymorphism, Single Nucleotide , Receptors, N-Methyl-D-Aspartate/genetics , Schizophrenia/genetics , 3' Untranslated Regions , Adult , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , Homozygote , Humans , Italy/epidemiology , Male , Molecular EpidemiologyABSTRACT
BACKGROUND: The GRIN1 gene plays a fundamental role in many brain functions, and its involvement in the pathogenesis of the schizophrenia has been widely investigated. Non-synonymous polymorphisms have not been identified in the coding regions. To investigate the potential role of GRIN1 in the susceptibility to schizophrenia, we analyzed the G1001C polymorphism located in the promoter region in a case-control association study. METHODS: The G1001C polymorphism allele distribution was analyzed in a sample of 139 Italian schizophrenic patients and 145 healthy control subjects by a polymerase chain reaction amplification followed by digestion with a restriction endonuclease. RESULTS: We found that the C allele may alter a consensus sequence for the transcription factor NF-kappa B and that its frequency was higher in patients than in control subjects (p =.0085). The genotype distribution also was different, with p =.034 (if C allele dominant, p =.0137, odds ratio 2.037, 95% confidence interval 1.1502-3.6076). CONCLUSIONS: The association reported in this study suggests that the GRIN1 gene is a good candidate for the susceptibility to schizophrenia.
