The comprehensive study of the dopamine transporter gene function

一些精神疾病似乎与大脑多巴胺系统的功能障碍有关。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端，因此DAT基因的表达似乎控制着多巴胺能神经元的传递。由于可卡因、安非他明、苯环利定和1-甲基-4-苯基吡啶（MPP）等精神药物与DAT结合，DAT基因将成为药物滥用的目标之一。本研究小组研究发现，人类多巴胺转运蛋白基因（DAT1）在其基因2319G/ a的3'-UTR中存在可变数量的串联重复序列（VNTR），并且该多态性在单倍型分析中与g2319a和VNTR多态性存在显著关联。在本研究中，我在DAT基因的5'侧区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的分析，两种多态性似乎都是功能性的，因此我研究了对照组（n=106）和酗酒者（n=182）之间的关联研究。不幸的是，我没有发现它们之间的任何意义，因此需要进一步的研究。

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.