Evidence that the N-methyl-D-aspartate subunit 1 receptor gene (GRIN1) confers susceptibility to bipolar disorder
Open Access
- 1 February 2003
- journal article
- research article
- Published by Springer Nature in Molecular Psychiatry
- Vol. 8 (2), 241-245
- https://doi.org/10.1038/sj.mp.4001218
Abstract
There is evidence for the involvement of glutamatergic transmission in the pathogenesis of major psychoses. The two most commonly used mood stabilizers (ie lithium and valproate) have been found to act via the N-methyl-D-aspartate receptor (NMDAR), suggesting a specific role of NMDAR in the pathogenesis of bipolar disorder (BP). The key subunit of the NMDAR, named NMDA-1 receptor, is coded by a gene located on chromosome 9q34.3 (GRIN1). We tested for the presence of linkage disequilibrium between the GRIN1 (1001-G/C, 1970-A/G, and 6608-G/C polymorphisms) and BP. A total of 288 DSM-IV Bipolar I, Bipolar II, or schizoaffective disorder, manic type, probands with their living parents were studied. In all, 73 triads had heterozygous parents for the 1001-G/C polymorphism, 174 for the 1970-A/G, and 48 for the 6608-G/C. These triads were suitable for the final analyses, that is, the transmission disequilibrium test (TDT) and the haplotype-TDT. For the 1001-G/C and the 6608-G/C polymorphisms, we found a preferential transmission of the G allele to the affected individuals (χ2=4.765, df=1, P=0.030 and χ2= 8.395, df=1, P=0.004, respectively). The 1001G-1970A-6608A and the 1001G-1970A-6608G haplotypes showed the strongest association with BP (global χ2=14.12, df=4, P=0.007). If these results are replicated there could be important implications for the involvement of the GRIN1 in the pathogenesis of BP. The role of the gene variants in predicting the response to mood stabilizers in BP should also be investigated.Keywords
This publication has 28 references indexed in Scilit:
- Genetics of bipolar disorderJournal of Medical Genetics, 1999
- No association of the tryptophan hydroxylase gene with bipolar affective disorder, unipolar affective disorder, or suicidal behaviour in major affective disorderAmerican Journal of Medical Genetics, 1998
- Serotonin transporter (5-HTT) gene and bipolar affective disorderAmerican Journal of Medical Genetics, 1998
- Association analysis of the 5-HT2C receptor and 5-HT transporter genes in bipolar disorderAmerican Journal of Medical Genetics, 1997
- Serotonin2A receptor gene polymorphism in mood disordersBiological Psychiatry, 1997
- Association study of bipolar disorder with candidate genes involved in catecholamine neurotransmission: DRD2, DRD3, DAT1, and TH genesAmerican Journal of Medical Genetics, 1996
- Serotonin Receptor SubtypesCNS Drugs, 1995
- The role of dopamine in mood disordersComprehensive Psychiatry, 1992
- Serotonergic Dysfunction in DepressionThe British Journal of Psychiatry, 1989
- The Genetics of Depression and Manic-Depressive DisorderThe British Journal of Psychiatry, 1989