1995 Fiscal Year Final Research Report Summary
Identification of genes associated with susceptibility to schizophrenia
| Project/Area Number |
06454606
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human genetics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
HAMAGUCHI Hideo Univ.of Tsukuba, Institute of Basic Medical Sciences Professor, 基礎医学系, 教授 (00091918)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Kimiko Univ.of Tsukuba, Institute of Basic Medical Sciences Associate Prof, 基礎医学系, 講師 (90215319)
ARINAMI Tadao Univ.of Tsukuba, Institute of Basic Medical Sciences Assis Prof, 基礎医学系, 助教授 (10212648)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Schizophrenia / dopamine D2 receptor / molecular variant / association / sequestration / promoter |
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| Research Abstract |
Dopamine D2 receptor variant, D2Cys311, a missense mutation changing serine 311 in the third intracellular loop to cysteine, and wild type, D2Ser311, were expressed stably in Chinese Ovary Cells and dopamine-induced sequestration was examined by measuring the loss of binding of the hydrophilic ligand sulpiride from the cell surface. A D2S (the short form isoform of dopamine D2 receptor) receptor variant containing Cys311 was found to be sequestered to a significantly smaller extent compared to wild-type D2S receptors, though sequestration of D2L (the long form isoform of D2 receptor) receptors was not so apparent as that of D2S receptors and no apparent difference was found between D2Ser311 and D2Sys311 in D2L receptors.
5' flanking region of the dopamine D2 receptor gene was examined to search for nucleotide variants. Two common polymorphic sites, A-584G and Ins/DelG-486, were found. Bmax values for spiperone binding in the putamen were not significantly different between postmortem brains with G-584 and those without it. Each allele frequency of A-584G polymorphism was not significantly different between schizophrenics and controls. Bmax values for spiperone binding in the putamen were marginally significantly higher in postmortem brains with the Ins allele (p<0.03) than in those without it. The Ins allele frequency was significantly frequent in schizophrenics whose age of onset younger than 35 than in controls (p<0.008). These results suggest that some variants in the dopamine D2 receptor gene are involved in susceptibility to some types of schizophrenia.
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