2003 Fiscal Year Final Research Report Summary
Association of genetic polymorphisms with psychotropic-response in mental disorders
| Project/Area Number |
13470198
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Fujita Health University |
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Principal Investigator |
OZAKI Norio Fujita Health University, School of Medicine, Professor, 医学部, 教授 (40281480)
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| Co-Investigator(Kenkyū-buntansha) |
SAWADA Makoto Fujita Health University, Institute for Comprehensive Medical Science, Professor, 総合医科学研究所, 教授 (10187297)
NAITOU Hiroshi Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (00247644)
IWATA Nakao Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (60312112)
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| Project Period (FY) |
2001 – 2003
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| Keywords | MOOD DISOREDERS / SCHIZOPHRENIA / ANXIETY DISORDERS / GENOME / PHARMACOGENETICS / ANTIPSYCHOTICS / SSRI |
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| Research Abstract |
The importance of genetic factors among inter-individual diversities of drug response has been steadily clarified. As a result, pharmacogenetics, which is defined as the science of pharmacological response and its modification by hereditary influence has been extensively carried out in order to clarify a marker of clinical response, put individualized medicine into a reality, and discover a new drug.
Thus, we carried out the following pharmacogenetic studies of psychotropics.
1.Risperidone response : D2 and 5-HT2A gene haplotype is associated with clinical efficacy of risperidone in schizophrenia.
2.SSRI response : Newly identified amino acid substitution in 5-HT transporter gene is associated with treatment resistant familiar obsessive compulsive disorder
3.Amphtamine response : VNTR polymorphism of the dopamine transporter gene is a risk factor for methamphetamine induced psychosis
We also elucidated the functional meanings of genetic polymorphism associated with mental disorders or treatment response.
1.Pro15Ser in 5-HT5A receptor gene associated with schizophrenia : The expression study using cultured cell revealed that atypical antipsychotics including zotepine, risperidone, clozpine have high affinity to 5-HT5A receptor and the Bmax of the Ser15 is about 50% of that of the Per15.
2.Cys23Ser in 5-HT2C receptor gene associated with Clozapine response : The expression study using cultured cell revealed that the Ser23 allele may be constitutively more active than Cys23l
We are going to continue pharmacogenetic studies of psychotropics to obtain a marker for the drug response and open the road to the development of a new drug.
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[Publications] Noda M, Yasuda S, Okada M, Higashida H, Shimada A, Iwata N, Ozaki N, Nishikawa K, Shirasawa S, Uchida M, Aoki S, Wada K: "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways."J Neurochem. 84(2). 222-232 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Ujike H, Harano M, Inada T, Yamada M, Komiyama T, Sekine Y, Sora I, Iyo M, Katsu T, Nomura A, Nakata K, Ozaki N: "Nine-or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis."Pharmacogenomics J. 3(4). 242-247 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Iwase T, Kajimura N, Uchiyama M, Ebisawa T, Yoshimura K, Kamei Y, Shibui K, Kim K, Kudo Y, Katoh M, Watanabe T, Nakajima T, Ozeki Y, Sugishita M, Hori T, Ikeda M, Toyoshima R, Inoue Y, Yamada N, Mishima K, Nomura M, Ozaki N, Okawa M, Takahashi K, Yamauchi T: "Mutation screening of the human Clock gene in circadian rhythm sleep disorders."Psychiatry Res. 109(2). 121-128 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Ebisawa T, Uchiyama M, Kajimura N, Mishima K, Kamei Y, Katoh M, Watanabe T, Sekimoto M, Shibui K, Kim K, Kudo Y, Ozeki Y, Sugishita M, Toyoshima R, Inoue Y, Yamada N, Nagase T, Ozaki N, Ohara O, Ishida N, Okawa M, Takahashi K, Yamauchi I: "Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome."EMBO Rep. 2(4). 342-346 (2001)
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「研究成果報告書概要(欧文)」より
