gene polymorphism of transporters as risk factors of Parkinson's disease

由于遗传因素和环境因素都被认为与帕金森氏症症状的发生有关，冰岛的大规模遗传调查清楚地表明了遗传因素。MPTP和6-羟基多巴胺是在制作模型或帕金森氏病时使用的，它们是通过突触间隙的多巴胺转运蛋白(DAT)被摄取的。因此，DAT基因是帕金森氏病可疑的有力候选者。在DAT基因的直接测序结果中，我们发现该基因的两个外显子有两个多态性。其中121.5个A/G变异存在于外显子9，在帕金森病组中以G为主。然而，这种核苷酸变异不会改变氨基酸，也不会直接改变DAT的功能。然后，用直接测序法搜索DAT基因启动子区域缩写1000bp的功能变异进行鉴定。在对这项研究做了充分的解释后，我们采集了24名散发性帕金森病患者的血液，并从血液中的白细胞中提取了DNA。结果发现Sp-1基因有10个多态，其中3个存在于Sp-1位点内部。这些多态性有望改变DAT的数量，并影响多巴胺能神经元的耗竭。

As both the hereditary factor and the environmental factor had been thought to be related to development of symptoms of Parkinson's disease, heredity factors were clearly shown by large-scale genetic investigation of Iceland. MPTP and 6-hydroxydopamine, which are used when making a model or Parkinson's disease, are uptaken through a dopamine transformer porter (DAT) from a synapse gap. Therefore, the DAT gene was a strong candidate for suspectivity of Parkinson's disease. In the results of direct sequencing analysis of the DAT gene, we found two polymorphism in exons in the gene. One of them, 121 5 A/G variation, exists in an exon 9. The G is dominant in the Parkinson's disease group. However this nucleotide variation does not change the amino acid, it does not directly change the function of the DAT. And then, we searched the functional variation of the promoter region abbreviation 1000bp of the DAT gene using the direct sequencing method for identification. After giving sufficient explanation about the research, we collected blood from 24 sporadic Parkinson's disease patients and extracted DNA from the leukocyte in the blood. In the results, we found 10 polymorphism and the three existed in the inside of Sp-1 site. These polymorphism will be expected to change the amount of DAT and to effect the depletion of the dopaminergic neurons.