新疆地区维吾尔族、汉族klotho基因单核苷酸多态性与特发性草酸钙肾结石相关性研究

项目名称： 新疆地区维吾尔族、汉族klotho基因单核苷酸多态性与特发性草酸钙肾结石相关性研究

项目编号： No.81460139

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 木拉提·马合木提

作者单位： 新疆医科大学

项目金额： 47万元

中文摘要： 临床上大多数特发性草酸钙肾结石无明显遗传背景和相关系统性疾病。Klotho对钙磷调节的重要作用已被确认，但在肾脏钙化及结石方面研究还不多见。有研究结果发现klotho缺失影响TRPV5通道对钙离子的重吸收，呈现出高血钙及高尿钙表现。提示由klotho协同TRPV5介导的钙在肾远曲小管/集合管的重吸收发生障碍。而Klotho能够激活TRPV5使其发挥正常功能。本课题将应用免疫组化、Western Blot及Real Time-PCR等技术，在动物和分子水平深入研究Klotho在肾脏钙化结石形成中的机制。另有研究发现Klotho基因的多态性与欧美人群肾结石的形成风险相关。本研究拟利用高分辨溶解曲线（HRM）检测等技术研究维吾尔族与汉族人群中Klotho基因多态性与特发性草酸钙肾结石疾病的相关性及其对肾脏钙化结石形成的作用机制。为阐明肾结石形成机制提供新的思路，为其防治策略提供新的实验数据和

中文关键词： 维吾尔族；汉族；草酸钙结石；klotho基因；单核苷酸多态性

英文摘要： Most clinically idiopathic calcium oxalate kidney stones has no significant genetic background and systemic diseases. Klotho is important for the regulation of calcium and phosphorus role has been confirmed, but the researchs of kidney calcification are still the exception. Researchs has found that the abscene of Klotho impair the reabsorbtion of calcium ions mediated by TRPV5,and present as hypercalcemia and hypercalciuria, this process needs the participation of klotho. Studies suggest that something may impair the reabsorption of calcium mediated by klotho in collaboration with TRPV5 in Kidney collecting tubule and Distal convoluted renal tubule. Our project will apply Immunohistochemistry, Western Blot and Real Time-PCR technology,and make a depth study of the mechanism of klotho in calcification in Kidney stone formation at animal and molecular level. Other studies also found that the klotho gene polymorphism was associated with the risk of Kidney stone formation in Europen, American and Japanese population.High Resolution Dissolved Curves will be used in our project to study the correlation of klotho gene mutation in Uighur and Han population and idiopathic calcium oxalate Kidney stone disease,and mechanism of calcification in Kidney stone formation caused by its variation.Our project will illustrate mechanism of the Kidney stone formation and provide new ideas for its prevention strategy and provides new experimental data and theoretical basis.

英文关键词： Uighur;Han;Gene polymorphism;Calcium oxalate stone;Klotho gene