Impact of mutations and polymorphisms in transporter families on population health

转运蛋白在生物物质的转运中起着至关重要的作用。我们把注意力集中在转运蛋白突变对人群健康的影响上。赖氨酸尿蛋白不耐受（LPI）是由碱性氨基酸转运蛋白SLC 7A 7突变引起的疾病。LPI可通过婴儿期的早期干预控制。它是岩手县的地方病，而在日本其他地区的流行率很低。因此，早期干预是岩手县特有的公共卫生问题之一。我们进行了遗传流行病学研究，发现SLC 7A 7中存在R41 OX突变的奠基者突变。LPI的过度流行归因于该创始者突变的高基因频率。我们开始了一项大规模筛查计划，使用分子诊断LPI。大规模筛查计划被证明是成本效益和可靠的诊断工具。我们还对当地的一组Osler-Rendu-Weber病、多囊肾和一种病因不明的甲状腺肿进行了遗传流行病学研究。我们试图在功能上评估突变的蛋白质，试图开发一种通用的方法来预测功能改变。在本研究中，我们以胰岛素原秋田突变为例进行了评估。遗传性疾病的患病率受到人口历史和社会制度的广泛干扰。有必要促进遗传流行病学和功能蛋白质组学的研究活动。

Transporters play crucial roles in transporting biological substances. We have focused our attention to the effects of mutations of transporters on population health.1. Lysinuric protein intolerance (LPI) was a disease caused by a mutation of basic amino acid transporter SLC7A7. LPI is controllable by early intervention at infancy. It is endemic in Iwate while its prevalence is very small in other areas in Japan. Its early intervention, therefore, is one of the public health issues specific to Iwate. We conduced genetic epidemiological study and had shown a founder mutation of R41OX mutation in SLC7A7. Excess prevalence of LPI was attributed to a high gene frequency of this founder mutation.2. We embarked a mass screening program using molecular diagnosis for LPI. The mass screening program turned out to be cost effective and reliable as a diagnosis tool.3. We also conducted genetic epidemiology in a local cluster of Osler-Rendu-Weber disease, polycystic Kidney and a local goiter unknown pathogenesis.4. We tried to evaluate functionally the mutated proteins in an attempt to develop a general methodology to predict ftinctional alterations. In this project, we evaluated mutations of proinsulin Akita as-an example.The prevalences of genetic diseases are very widely perturbed by the population history and social systems. It is necessary to promote research activities for genetic epidemiology and functional proteomics.