PMID- 19665356 OWN - NLM STAT- MEDLINE DCOM- 20091207 LR - 20160526 IS - 1573-2509 (Electronic) IS - 0920-9964 (Linking) VI - 114 IP - 1-3 DP - 2009 Oct TI - Exomic sequencing of the ionotropic glutamate receptor N-methyl-D-aspartate 3A gene (GRIN3A) reveals no association with schizophrenia. PG - 25-32 LID - 10.1016/j.schres.2009.07.005 [doi] AB - BACKGROUND: Growing evidence suggests that dysregulation of N-methyl-D-aspartate receptor (NMDAR)-mediated glutamate neurotransmission may be involved in the pathophysiology of schizophrenia. The NMDAR is a heteromeric protein complex consisting of subunits from three subfamilies (NR1, NR2A, 2B, 2C, 2D and NR3A, 3B). The unique ability of NR3A to modulate the NMDAR function makes it an attractive candidate gene of schizophrenia. The purpose of this study was to investigate the involvement of the gene encoding the human NR3A subunit (GRIN3A) in the liability to schizophrenia. METHODS: We searched for genetic variants in the putative core promoter region and all the exons (including UTR ends) of the GRIN3A gene in 333 Han Chinese patients with schizophrenia and 369 control subjects from Taiwan using direct polymerase chain reaction (PCR) autosequencing, and assessed their association with schizophrenia. RESULTS: We identified 22 single nucleotide polymorphisms (SNPs) in the GRIN3A gene in this sample. SNP- and haplotype-based analyses showed no association of these 22 SNPs with schizophrenia. Nevertheless, we identified two missense mutations (D133N and Q1091H), one nonsense mutation (R1024X), and two synonymous mutations (Y873Y and E889E) of the GRIN3A gene in 6 out of 333 (1.8%) patients, while no rare mutations were found in 369 control subjects (p=0.011, Fisher's exact test, one-tailed). In silico analysis showed that the R1024X and Q1091H mutations are possibly damaging. CONCLUSIONS: Although the functional significance of these mutations remains to be characterized, our study indicates that rare mutations in the GRIN3A gene may contribute to the pathogenesis of schizophrenia in certain patients. FAU - Shen, Yu-Chih AU - Shen YC AD - Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan; Department of Psychiatry, Tzu-Chi Medical Center and University, Hualien, Taiwan. FAU - Liao, Ding-Lieh AU - Liao DL FAU - Chen, Jen-Yeu AU - Chen JY FAU - Wang, Ying-Chieh AU - Wang YC FAU - Lai, I-Ching AU - Lai IC FAU - Liou, Ying-Jay AU - Liou YJ FAU - Chen, Yu-Jun AU - Chen YJ FAU - Luu, Sy-Ueng AU - Luu SU FAU - Chen, Chia-Hsiang AU - Chen CH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090807 PL - Netherlands TA - Schizophr Res JT - Schizophrenia research JID - 8804207 RN - 0 (Receptors, AMPA) RN - 0 (glutamate receptor ionotropic, AMPA 3) SB - IM MH - Adult MH - DNA Mutational Analysis MH - Exons/*genetics MH - Female MH - *Genetic Predisposition to Disease MH - Humans MH - Linkage Disequilibrium MH - Male MH - Middle Aged MH - Mutation/*genetics MH - Polymorphism, Single Nucleotide/*genetics MH - Receptors, AMPA/*genetics MH - Schizophrenia/*genetics MH - Taiwan EDAT- 2009/08/12 09:00 MHDA- 2009/12/16 06:00 CRDT- 2009/08/12 09:00 PHST- 2009/05/04 00:00 [received] PHST- 2009/06/27 00:00 [revised] PHST- 2009/07/04 00:00 [accepted] PHST- 2009/08/12 09:00 [entrez] PHST- 2009/08/12 09:00 [pubmed] PHST- 2009/12/16 06:00 [medline] AID - S0920-9964(09)00323-5 [pii] AID - 10.1016/j.schres.2009.07.005 [doi] PST - ppublish SO - Schizophr Res. 2009 Oct;114(1-3):25-32. doi: 10.1016/j.schres.2009.07.005. Epub 2009 Aug 7.