Association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia

• Published in: Biological psychiatry (1969) Vol. 53; no. 7; pp. 617 - 619
• Main Authors: Begni, Silvia, Moraschi, Stefania, Bignotti, Stefano, Fumagalli, Fabio, Rillosi, Luciana, Perez, Jorge, Gennarelli, Massimo
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2003; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; association; Biological and medical sciences; Biotechnology; Carrier Proteins - genetics; Disease Susceptibility; Female; functional polymorphism; Fundamental and applied biological sciences. Psychology; Genetic technics applied to diagnosis; GRIN1; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; ionotropic glutamate receptor; Male; Medical sciences; Nerve Tissue Proteins - genetics; Polymerase Chain Reaction; Polymorphism, Genetic; promoter region; Promoter Regions, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Schizophrenia - genetics; ionotropic glutamate receptor; Schizophrenia; promoter region; association; functional polymorphism; GRIN1; Human; Ionotropic receptor; Transcription promoter; Etiopathogenesis; Exploration; Genotype; Glutamate receptor; Psychosis; Polymerase chain reaction; Allele; Gene; Genetics; Molecular biology; Polymorphism
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(02)01783-3

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. 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. We found that the C allele may alter a consensus sequence for the transcription factor NF-κB 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). The association reported in this study suggests that the GRIN1 gene is a good candidate for the susceptibility to schizophrenia.