Genetic analysis of transporters and channels related to urolithiasis or hydronephrosis

与尿石症或肾积水相关的转运蛋白和通道的遗传分析

• 批准号: 13671101
• 负责人: SEKINE Takashi
• 金额: $ 2.3万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671101/
• 关键词: urolithiasis; human uric acid transporter 1; chrolide channel 5; epithelial calcium channel; genetic analsysis

In this project, we performed the following three investigations related to urolithiasis.(1) Genetic analysis of ECaC1 (epithelial calcium channnel 1) gene in patients with idiopathic hypercalciuria(2) Genetic analysis of hURAT1 (human uirnc acid transporter 1) gene in patients with hereditary hypouricemia(3) Genecitc analysis of CLCN5 (chloride channel 5) in patients with Dent's disease.During 2 years of investigation, we could obtain the following results :(1) We could not detect any mutations in ECaC1 gene in patiesnts with idiopathic hypercalciuria who developed urolithiasis during infancy.(2) We performed genecic analyzes in 7 unrelated Japanese families with renal hypouricemia. We identified hURAT1 mutations in 6 families ; in five families, W258X mutation was detected. This result indicates that W258X mutation is the predominant genetic cause in Japanese patients with renal hypouricemia.(3) We performed CLCN5 gene analysis in more than 15 families with Dent's disease, and identified several mutations.Now, we continue to perform genetic analysis of CLCN5 and hURAT1. The present results added certain knowledge on the genetic backgrounds of urolithiasis.

在这个项目中，我们进行了以下三项与尿石症相关的研究。(1)ECaC1的遗传分析特发性高钙尿症患者上皮钙通道1基因（2）hURAT1基因分析遗传性低尿酸血症患者的人尿酸转运体1基因（3）CLCN 5基因的检测在2年的研究中，我们可以获得以下结果：（1）在婴儿期发生尿石症的特发性高钙尿症患者中未检测到ECaC1基因突变。(2)我们在7个无关的日本肾性低尿酸血症家族中进行了基因分析。在6个家系中检测到hURAT1突变，5个家系中检测到W258X突变。这一结果表明，W258X突变是日本肾性低尿酸血症患者的主要遗传原因。(3)我们在超过15个Dent病家系中进行了CLCN 5基因分析，发现了几个突变。现在，我们继续进行CLCN 5和hURAT 1的遗传分析。本研究结果增加了对尿石症遗传背景的认识。

项目成果

Enomoto A, et al.: "Role of organic anion transporters in the tubular transport of indoxyl sulfate and the induction of its nephrotoxicity"J. Am Soc Nephrol. 13. 1711-1720 (2002)

Enomoto A 等人：“有机阴离子转运蛋白在硫酸吲哚酚肾小管转运中的作用及其肾毒性的诱导”J。

Takeda M., Khamdang S., Narikawa S., Kimura H., Hosoyamada M., Cha SH., Sekine T., Endou H: "Characterization of methotrexate transport and its drug interactions with human organic anion transporters"J.Pharmacol.Exp.Ther. 302(2). 666-671 (2002)

Takeda M.、Khamdang S.、Narikawa S.、Kimura H.、Hosoyamada M.、Cha SH.、Sekine T.、Endou H：“甲氨蝶呤转运的表征及其与人体有机阴离子转运蛋白的药物相互作用”J.Pharmacol。

Kojima R, Sekine T.et al.: "Immunolocalization of multispecific organic anion transporters, OAT1, OAT2, and OAT3, in rat kidney"J Am Soc Nephrol. 13. 848-857 (2002)

Kojima R、Sekine T.等人：“大鼠肾脏中多特异性有机阴离子转运蛋白、OAT1、OAT2 和 OAT3 的免疫定位”J Am Soc Nephrol。

Kobayashi Y, Hirokawa N, Ohshiro N, Sekine T. Sasaki T, Tokuyama S, Endou H, Yamamoto T.: "Differential gene expression of organic anion transporters in male and female rats"Biochem Biophys Res Commun. 290(1). 482-487 (2002)

Kobayashi Y、Hirokawa N、Ohshiro N、Sekine T. Sasaki T、Tokuyama S、Endou H、Yamamoto T.：“雄性和雌性大鼠有机阴离子转运蛋白的差异基因表达”Biochem Biophys Res Commun。

Enomot A et al.: "Molecular identification of a renal urate-anion exchanger that regulate blood urate levels Nature"Nature. 417. 447-452 (2002)

Enomot A 等人：“调节血尿酸水平的肾脏尿酸阴离子交换剂的分子鉴定”自然。