PMID- 12610658
OWN - NLM
STAT- MEDLINE
DCOM- 20030923
LR  - 20041117
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 8
IP  - 2
DP  - 2003 Feb
TI  - Evidence that the N-methyl-D-aspartate subunit 1 receptor gene (GRIN1) confers 
      susceptibility to bipolar disorder.
PG  - 241-5
AB  - 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 
      (chi(2)=4.765, df=1, P=0.030 and chi(2)= 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 chi(2)=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.
FAU - Mundo, E
AU  - Mundo E
AD  - Neurogenetics Section, Centre for Addiction and Mental Health (CAMH), Department 
      of Psychiatry, University of Toronto, Clarke Site R-31, Toronto, Ontario, Canada 
      M5T 1R8.
FAU - Tharmalingham, S
AU  - Tharmalingham S
FAU - Neves-Pereira, M
AU  - Neves-Pereira M
FAU - Dalton, E J
AU  - Dalton EJ
FAU - Macciardi, F
AU  - Macciardi F
FAU - Parikh, S V
AU  - Parikh SV
FAU - Bolonna, A
AU  - Bolonna A
FAU - Kerwin, R W
AU  - Kerwin RW
FAU - Arranz, M J
AU  - Arranz MJ
FAU - Makoff, A J
AU  - Makoff AJ
FAU - Kennedy, J L
AU  - Kennedy JL
LA  - eng
PT  - Journal Article
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Adult
MH  - Bipolar Disorder/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Humans
MH  - *Linkage Disequilibrium
MH  - Male
MH  - Polymorphism, Genetic
MH  - Receptors, N-Methyl-D-Aspartate/*genetics
EDAT- 2003/03/01 04:00
MHDA- 2003/09/25 05:00
CRDT- 2003/03/01 04:00
PHST- 2003/03/01 04:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/03/01 04:00 [entrez]
AID - 4001218 [pii]
AID - 10.1038/sj.mp.4001218 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2003 Feb;8(2):241-5. doi: 10.1038/sj.mp.4001218.