A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia
Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human ch...
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| Published in | Schizophrenia research Vol. 101; no. 1-3; pp. 9 - 16 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Amsterdam
Elsevier B.V
01.04.2008
Elsevier Science |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0920-9964 |
| DOI | 10.1016/j.schres.2008.01.027 |
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| Abstract | Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage analysis to contain a susceptibility locus for schizophrenia.
We screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese patients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the influence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected cells.
Twenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a synonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients with schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity between the T and C alleles.
Our results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia. |
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| AbstractList | Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage analysis to contain a susceptibility locus for schizophrenia.
We screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese patients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the influence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected cells.
Twenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a synonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients with schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity between the T and C alleles.
Our results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia. Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage analysis to contain a susceptibility locus for schizophrenia.INTRODUCTIONGlutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage analysis to contain a susceptibility locus for schizophrenia.We screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese patients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the influence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected cells.METHODSWe screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese patients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the influence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected cells.Twenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a synonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients with schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity between the T and C alleles.RESULTSTwenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a synonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients with schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity between the T and C alleles.Our results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia.CONCLUSIONSOur results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia. Introduction: Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate\nreceptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the\nhuman central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage\nanalysis to contain a susceptibility locus for schizophrenia.\nMethods: We screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese\npatients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the\ninfluence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected\ncells.\nResults: Twenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a\nsynonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients\nwith schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity\nbetween the T and C alleles.\nConclusions: Our results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to\nschizophrenia. AbstractIntroductionGlutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage analysis to contain a susceptibility locus for schizophrenia. MethodsWe screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese patients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the influence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected cells. ResultsTwenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a synonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients with schizophrenia and 2382 Japanese control subjects (allelic p= 0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity between the T and C alleles. ConclusionsOur results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia. |
| Author | Arai, Makoto Iritani, Shyuji Itokawa, Masanari Ozaki, Norio Koga, Minori Watanabe, Yuichiro Ishiguro, Hiroki Someya, Toshiuki Niizato, Kazuhiro Horiuchi, Yasue Ujike, Hiroshi Iwata, Nakao Kunugi, Hiroshi Ohtsuki, Tsuyuka Inada, Toshiya Arinami, Tadao |
| Author_xml | – sequence: 1 givenname: Tsuyuka surname: Ohtsuki fullname: Ohtsuki, Tsuyuka organization: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan – sequence: 2 givenname: Minori surname: Koga fullname: Koga, Minori organization: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan – sequence: 3 givenname: Hiroki surname: Ishiguro fullname: Ishiguro, Hiroki email: hishigur@md.tsukuba.ac.jp organization: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan – sequence: 4 givenname: Yasue surname: Horiuchi fullname: Horiuchi, Yasue organization: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan – sequence: 5 givenname: Makoto surname: Arai fullname: Arai, Makoto organization: Department of Schizophrenia Research, Tokyo Institute of Psychiatry, Tokyo 156-8585, Japan – sequence: 6 givenname: Kazuhiro surname: Niizato fullname: Niizato, Kazuhiro organization: Tokyo Metropolitan Matsuzawa Hospital, Department of Psychiatry, Tokyo 156-0057, Japan – sequence: 7 givenname: Masanari surname: Itokawa fullname: Itokawa, Masanari organization: Department of Schizophrenia Research, Tokyo Institute of Psychiatry, Tokyo 156-8585, Japan – sequence: 8 givenname: Toshiya surname: Inada fullname: Inada, Toshiya organization: Department of Psychiatry, Teikyo University School of Medicine, Chiba Medical Center, Anesaki 3426-3, Ichihara-shi, Chiba 299-0111 Japan – sequence: 9 givenname: Nakao surname: Iwata fullname: Iwata, Nakao organization: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan – sequence: 10 givenname: Shyuji surname: Iritani fullname: Iritani, Shyuji organization: Department of Psychiatry, School of Medicine, Nagoya University, Nagoya 466-8550, Aichi, Japan – sequence: 11 givenname: Norio surname: Ozaki fullname: Ozaki, Norio organization: Department of Psychiatry, School of Medicine, Nagoya University, Nagoya 466-8550, Aichi, Japan – sequence: 12 givenname: Hiroshi surname: Kunugi fullname: Kunugi, Hiroshi organization: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan – sequence: 13 givenname: Hiroshi surname: Ujike fullname: Ujike, Hiroshi organization: Department of Neuropsychiatry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan – sequence: 14 givenname: Yuichiro surname: Watanabe fullname: Watanabe, Yuichiro organization: Department of Psychiatry, Niigata University Graduate School of Medical and Denatal Sciences, Niigata 951-8510, Japan – sequence: 15 givenname: Toshiuki surname: Someya fullname: Someya, Toshiuki organization: Department of Psychiatry, Niigata University Graduate School of Medical and Denatal Sciences, Niigata 951-8510, Japan – sequence: 16 givenname: Tadao surname: Arinami fullname: Arinami, Tadao organization: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan |
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| Keywords | Glutamate Expression Luciferase Prefrontal Social environment Human Enzyme Central nervous system Schizophrenia Glutamate receptor Prefrontal cortex Case control study Gene expression Genetic determinism Encephalon Psychosis Metabotropic receptor Excitatory aminoacid Neurotransmitter Genetics Candidate gene Oxidoreductases Mutation Polymorphism |
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| Snippet | Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled... AbstractIntroductionGlutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are... Introduction: Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate\nreceptors (mGluRs) are... |
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| SubjectTerms | Adult Adult and adolescent clinical studies Biological and medical sciences Case-Control Studies Expression Female Gene Frequency Genetic Predisposition to Disease Genotype Glutamate Humans Luciferase Male Medical sciences Middle Aged Polymorphism, Genetic - genetics Prefrontal Psychiatric/Mental Health Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Receptors, Metabotropic Glutamate - genetics Schizophrenia Schizophrenia - genetics |
| Title | A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia |
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