Gene therapy for familial amybidotic polyneuropathy by urtra-fundaoning artificial nucleic acids

众所周知，瑞典的FAP患者的表型与其他国家的FAP患者有很大的不同。为了阐明原因，我们进行了以下研究。1.瑞典北部实况调查：共有神经科、眼科等8名内科医生赴瑞典北部考察患者的临床表现和生活方式。2.痕量金属研究：采集池塘水、河井水、自来水管道水，测定水中12种金属元素。3.单倍型研究：将瑞典FAP患者的单倍型与其他国家FAP患者的单倍型进行比较，结果表明，水中金属As浓度高于日本样本。在明年的这个项目中，AS对体外淀粉样蛋白形成的影响将在我们的淀粉样蛋白形成检测系统中进行检测。在临床表现方面，不出所料，大多数患者起病晚，临床表现非常轻微。在单倍型研究中，瑞典的FAP患者样本与日本、葡萄牙和西班牙的FAP患者样本在几个基因上显示出不同的单倍型，这表明除了环境因素的影响外，遗传背景的差异可能部分解释了表型差异。在这些点上，我们将在明年继续我们的研究项目。

It is well known that the phenotype of Swedish FAP patients is quite different from that in other countries' FAP patients. To elucidate the reason, we performed the following studies. 1.Fact-finding study in northern part of Sweden : totally 8 medical doctors, such as neurologists and ophthalmologists went to northern part of Sweden to check clinical manifestations of the patients and way of living. 2.Trace metal study : Water in pond, river well, and water from water pipes were collected to measure 12 metals in water. 3.Haplotype study : Haplotypes of Swedish FAP patients were compared with those in other countries' FAP patients.By the studies, of metals in water, As concentrations were extremely higher compared with those in Japanese samples. In this project in next year, effect of As on amyloid formation in vitro will be examined in our amyloid formation assay system. Concerning clinical manifestations, as we expected, most of the patients was late-onset, and clinical manifestations were very mild. In the haplotype study, Swedish FAP patient samples showed different haplotypes in several genes compared with those in Japanese, Portugal, and Spanish FAP patients, suggesting that inaddition to the effect by environmental factors, the difference of the genetic background may partially explain the phenotype difference.In these points we continue our research projects in the next year.