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

转运蛋白基因多态性是帕金森病的危险因素

• 批准号: 12670605
• 负责人: KAWAKAMI Hideshi
• 金额: $ 2.18万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670605/
• 关键词: Parkinson's disease; dopamine transporter; genetic polymorphism; genetic factor; トランスポーター; 一塩基置換; ドーパミン

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.

由于遗传因素和环境因素都被认为与帕金森病症状的发展有关，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，用于制作模型或帕金森氏病，通过多巴胺Transformer porter（DAT）从突触间隙摄取。因此，DAT基因是一个强有力的候选人怀疑帕金森病。在DAT基因的直接测序分析结果中，我们发现该基因的外显子存在两个多态性。其中121 5 A/G变异存在于第9外显子。帕金森病组中G占主导地位。然而这种核苷酸变异并不改变DAT的氨基酸序列，也不直接改变DAT的功能。然后，我们利用直接测序法对DAT基因启动子区缩写1000 bp的功能变异进行了搜索鉴定。在对本研究进行充分说明后，我们采集了24例散发性帕金森病患者的血液，并从血液中的白细胞中提取DNA。结果发现10个多态性位点，其中3个位于Sp-1位点内部。预期这些多态性将改变DAT的量并影响多巴胺能神经元的消耗。

项目成果

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Oda M：“脑啡肽酶基因中的二核苷酸重复多态性与散发性阿尔格海默病无关”《神经科学快报》320・1-107（2002）。

Izumi Y: "Geneticp stadies in Parkinson's desease with an alpha-synudem/NACP gene polyanorphisin in Japan"Neuroscience Letters. 300・2. 125-127 (2001)

Izumi Y：“日本使用 α-synudem/NACP 基因多诺菲辛进行的帕金森病研究”《神经科学快报》300・2（2001 年）。

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Kumagai R：“脊髓小脑共济失调 6 型的电生理学研究：统计方法。”Neuroreport 11・5 (2000)。

Izumi Y, Morino H, Oda M, Maruyama H, Udaka F, Kameyama M, Nakamura S, Kawakami H: "Genetic studies in Parkinson's disease with an alpha-synuclein/NACP gene polymorphism in Japan"Neurosci Lett.. 300 (2). 125-127 (2001)

Izumi Y、Morino H、Oda M、Maruyama H、Udaka F、Kameyama M、Nakamura S、Kawakami H：“日本 α-突触核蛋白/NACP 基因多态性帕金森病的遗传学研究”Neurosci Lett.. 300 (2)

Morino H: "A single nucleotide polymorphism of dopamine transporter gene is associated with Parkinson's disease."Ann Neurol. 47・20. 528-531 (2000)

Morino H：“多巴胺转运蛋白基因的单核苷酸多态性与帕金森病有关。”Ann Neurol 47・20（2000）。