The comprehensive study of the dopamine transporter gene function

有些精神疾病似乎是以大脑多巴胺系统功能障碍为基础的。多巴胺转运体（DAT）是一种多巴胺特异性单胺转运体，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、苯丙胺、苯环己哌啶和1-甲基-4-苯基吡啶（MPP）等精神药物与DAT结合，DAT基因可能成为药物滥用的靶点之一。本课题组首次报道了人多巴胺转运蛋白基因（DAT 1）在其3 '-UTR区存在一个可变数目的串联重复序列（VNTR），即2319 G/A，并在单倍型分析中发现该多态性与G2319 A-和VNTR-多态性之间存在显著关联。本研究在DAT基因5 '端侧翼区发现了两个新的多态性位点，-1173C/G和-843C/T。由于计算机转录因子搜索程序的分析，两种多态性似乎都是功能性的，因此我研究了对照受试者（n=106）和酗酒受试者（n=182）之间的关联研究。不幸的是，我找不到它们之间有任何意义，结论是需要进一步的研究。

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.