Association of genetic polymorphisms with psychotropic-response in mental disorders

遗传多态性与精神疾病精神治疗反应的关联

• 批准号: 13470198
• 负责人: OZAKI Norio
• 金额: $ 9.22万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470198/
• 关键词: MOOD DISOREDERS; SCHIZOPHRENIA; ANXIETY DISORDERS; GENOME; PHARMACOGENETICS; ANTIPSYCHOTICS; SSRI; 遺伝子; 精神障害; 薬物反応性; 多型

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 disorder3.Amphtamine response : VNTR polymorphism of the dopamine transporter gene is a risk factor for methamphetamine induced psychosisWe 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 Cys23lWe 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.

在药物反应的个体多样性中，遗传因素的重要性已稳定地阐明。结果，已广泛进行了药物遗传学，该药物遗传学被定义为药理学反应的科学及其对遗传影响的修改，以澄清临床反应的标志，将个性化药物置于现实中，并发现一种新药物。 。 1.Pro15s.pro15ser在5-HT5A受体基因中与精神分裂症相关的：使用培养细胞的表达研究表明，包括Zotepine，Risperidone，Risperidone，Risperidone，Risperidone，Risperidone，Risperidone，Risperidone，Risperidone，Risperidone，clozpine高亲和力对5-HT5A受体和Ser15的BMAX的亲和力高约50％。与氯氮平反应相关的：使用培养细胞的表达研究表明，Ser23等位基因可能比Cys23LWe更具组成症的活性，将继续对精神药物进行药物遗传学研究，以获得药物反应的标志物，并为开发新药物的发展开辟了道路。

项目成果

Ozaki N(分担執筆): "Psychophamacogenetics, in ENCYCLOPEDIA OF THE HUMAN GENOME, vol 4"Macmillan Publishers Ltd, Nature Publishing Group. 917-922 (2003)

Ozaki N（贡献者）：“Psychophamacogenics，in ENCYCLOPEDIA OF THE HUMAN GENOME，第 4 卷”Macmillan Publishers Ltd，自然出版集团 917-922 (2003)。

Okada M, et al.: "Pepstatin A induces extracellular acidification distinct from aspartic protease inhibition in microglial cell line."Glia. 43(2). 167-174 (2003)

Okada M 等人：“胃酶抑素 A 诱导细胞外酸化，与小胶质细胞系中的天冬氨酸蛋白酶抑制不同。”

Suzuki, T, Ozaki, N et al.: "Association of Novel Genetic Variants in the Serotonin 5-HT4 Receptor Gene (HTR4) with Japanese Schizophrenia"Am J Med Genet. (In press).

Suzuki, T, Ozaki, N 等人：“血清素 5-HT4 受体基因 (HTR4) 中的新型遗传变异与日本精神分裂症的关联”Am J Med Genet。

Yamanouchi, Y, Ozaki, N et al.: "Effects of DRD2, 5-HT2A, and COMT Genes on Risperidone Treatment Response"The Pharmacogenomics Journal. (In press).

Yamanouchi, Y, Ozaki, N 等人：“DRD2、5-HT2A 和 COMT 基因对利培酮治疗反应的影响”药物基因组学杂志。

Hirano S, Sato T, Narita T, Kusunoki K, Ozaki N, Kimura S, Takahashi T, Sakado K, Uehara T: "Evaluating the state dependency of the Temperament and Character Inventory dimensions in patients with major depression: a methodological contribution."J Affect D

Hirano S、Sato T、Narita T、Kusunoki K、Ozaki N、Kimura S、Takahashi T、Sakado K、Uehara T：“评估重度抑郁症患者气质和性格量表维度的状态依赖性：方法论贡献。”