The comprehensive study of the dopamine transporter gene function

多巴胺转运蛋白基因功能的综合研究

• 批准号: 13671012
• 负责人: UENO Shu-ichi
• 金额: $ 2.3万
• 依托单位: The University of Tokushima (2002)Ehime University (2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671012/
• 关键词: dopamine transporter; association study; SNP type polymorphism; transcnption factor; alcoholism; VNTR多型; ハプロタイプ解析; 遺伝子発現

Some psychiatric disorders seem to have a basis in a dysfunction of the brain dopamine systems. Dopamine transporter (DAT) is a dopamine specific monoamine transporter that acts to take released dopamine back up into presynaptic terminals, so DAT gene expression seems to control the transmission of dopaminergic neurons. Since psyshotropic agents such as cocaine, amphetamine, phencyclidine and 1-methyl-4-phenylpyridinium (MPP) bind to DAT, DAT gene would be one of the targets for substance abuse. Our group fas reported that human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3'-UTR of the DAT1 gene, 2319G/A, and a significant association between this polymorphism in the haplotype analysis with G2319A-and VNTR-polymorphisms. In this study, I found two novel polymorphisms in the 5'-flanking region of DAT gene, -1173C/G and -843C/T. since both polymorphisms seem to be functional because of the analisis with a computer transcription factor search program, I studied the association study between control subjects (n=106) and alcoholic subjects (n=182). Unfortunately, I could not find any significance between them concluded that further studies will be needed.

一些精神疾病似乎与大脑多巴胺系统功能障碍有关。多巴胺转运蛋白 (DAT) 是一种多巴胺特异性单胺转运蛋白，其作用是将释放的多巴胺带回突触前末梢，因此 DAT 基因表达似乎控制多巴胺能神经元的传递。由于可卡因、安非他明、苯环己哌啶和 1-甲基-4-苯基吡啶鎓 (MPP) 等精神药物与 DAT 结合，因此 DAT 基因将成为药物滥用的目标之一。我们的 fas 小组报道，人多巴胺转运蛋白基因 (DAT1) 在 DAT1 基因的 3'-UTR 2319G/A 中具有可变数量的串联重复序列 (VNTR)，并且单倍型分析中的该多态性与 G2319A 和 VNTR 多态性之间存在显着关联。在这项研究中，我在DAT基因的5'侧翼区域发现了两个新的多态性，-1173C/G和-843C/T。由于通过计算机转录因子搜索程序进行分析，这两种多态性似乎都具有功能，因此我研究了对照受试者（n = 106）和酒精受试者（n = 182）之间的关联研究。不幸的是，我无法发现它们之间有任何意义，因此得出结论，需要进一步研究。

项目成果

Shu-ichi Ueno, Akira Sano: "Dopamine transporter"Pharmacodynamics,function and genetic polymorphisms. 420-428 (2001)

Shu-ichi Ueno，Akira Sano：“多巴胺转运蛋白”的药效学、功能和遗传多态性。