Klotho基因与骨质疏松研究进展

发布时间：2018-01-30 09:12

本文关键词： klotho 骨质疏松基因多态性 FGF23　出处：《重庆医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：Klotho基因是一种与衰老相关的基因,研究表明KL基因缺陷鼠可加快皮肤老化、肌肉萎缩、动脉硬化、骨质疏松等衰老过程。而骨质疏松主要是一种以骨量降低和骨微结构破坏为特征,导致骨脆性增加,易发生骨折的全身性骨病。研究表明骨质疏松有强大的基因背景；多项研究表明不同种族之间Klotho基因多态性与骨质疏松存在联系,目前研究发现的与骨密度有关KL基因的单核苷酸多态性基因有G395A、C1818T、F352V,以上基因多态性的研究是在不同人种、性别、生理状态下得出的结论。近16年来研究发现,KL基因通过各种途径参与骨质疏松发生、发展。首先KL作为一种FGFR 1c (111c)的辅助因子参与FGF23信号转导过程及调节甲状旁腺素的分泌。其次KL可以干扰胰岛素及类胰岛素生长因子-1的细胞内信号转导,另外KL类似于p-葡萄糖苷酸酶与TRPV5的糖基结合而激活TRPV5离子通道,从而调节肾对钙、磷吸收。该基因从分子水平、信号通路等方面参与骨代谢的调节,通过调节与骨代谢相关的钙、磷、活性维生素D3参与骨形成与骨吸收；该文就Klotho基因多态性、Klotho与钙磷代谢、骨代谢等方面与骨质疏松相关研究做一综述。
[Abstract]:Klotho gene is a kind of gene associated with aging. Studies have shown that KL gene deficient mice can accelerate skin aging, muscle atrophy, and arteriosclerosis. Osteoporosis and other aging processes. Osteoporosis is mainly characterized by the reduction of bone mass and the destruction of bone microstructure, resulting in an increase in bone brittleness. Fracture prone to systemic bone disease. Studies have shown that osteoporosis has a strong genetic background; Several studies have shown that Klotho gene polymorphisms are associated with osteoporosis among different ethnic groups. G395A is the single nucleotide polymorphism gene associated with bone mineral density (BMD). The study of C1818TF352V gene polymorphism is based on the conclusion of different race, sex and physiological state. It has been found in the last 16 years. KL gene is involved in osteoporosis through a variety of pathways. Development. First KL as a FGFR 1c / 111c). Second, KL interferes with the intracellular signal transduction of insulin and insulin-like growth factor-1. In addition, KL is similar to p- glucuronidase binding to the glycosyl group of TRPV5 and activates the TRPV5 ion channel, thereby regulating the absorption of calcium and phosphorus in the kidney. Signal pathway is involved in the regulation of bone metabolism, and calcium, phosphorus and active vitamin D3 are involved in bone formation and bone resorption by regulating the calcium, phosphorus and active vitamin D3 related to bone metabolism. This article reviews the relationship between Klotho gene polymorphism Klotho and calcium and phosphorus metabolism, bone metabolism and osteoporosis.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R580

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