胰岛素抵抗相关基因多态性在铁过载参与妊娠期糖尿病发生发展中的作用

项目名称： 胰岛素抵抗相关基因多态性在铁过载参与妊娠期糖尿病发生发展中的作用

项目编号： No.81471469

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 程海东

作者单位： 复旦大学

项目金额： 73万元

中文摘要： 妊娠期糖尿病（GDM）对于母婴的危害众所周知，越来越多的证据显示，孕期盲目补铁造成机体铁过载可能参与GDM的发生发展，但其机制尚不明确。胰岛素抵抗在妊娠期糖尿病的发病机制中起着重要作用。结合国内外报道及本课题组前期研究结果，我们假设胰岛素抵抗相关基因多态性是铁过载参与GDM发生发展的重要原因之一。本项目拟通过对GDM和非GDM孕妇胰岛素抵抗相关基因突变及基因多态性分析，明确不同SNP分型与铁代谢水平和GDM的关系；再通过体外细胞培养和动物实验，研究目标基因SNP差异在母体内可能通过何种方式导致肌肉、脂肪、胎盘细胞等出现糖代谢功能异常的。本项目旨在阐明胰岛素抵抗相关基因多态性在铁过载导致GDM发生发展中所起的作用，认识基因和环境的交互作用，倡导根据孕妇对铁的需求、状态及其自身基因多态性的差异指导孕期合理补铁，预防妊娠期糖尿病的发生。

中文关键词： 妊娠期糖尿病；铁；胰岛素抵抗；基因多态性；发病机制

英文摘要： It is known to all that gestational diabetes mellitus (GDM) do harm to maternal and infant health. Nowadays, clinical and epidemiological investigation indicated that iron overloading caused by iron supplementation blindly could affect glucose metabolism of mother, then increasing the risk of developing gestational diabetes mellitus (GDM). But the mechanism is indefinite. Insulin resistance plays an important role in the pathogenesis of gestational diabetes mellitus. According to the domestic and abroad reports and our previous research results, we hypothesized that insulin resistance related gene polymorphism is participated in development of GDM by iron overload. This project intends to analyze mutation and polymorphism of insulin resistance related gene from GDM and non GDM maternal, to explore relationship between different subtype of SNP and iron metabolism level. Then study how do the differences of target gene SNP to cause abnormal glucose metabolism by in vitro cell culture and animal experiments. This project aims to clarify the role of insulin resistance related gene polymorphism in the pathogenesis of GDM by iron overload, understanding interaction of genes and the environment. We initiated that doctors should make medicine advice of iron supplementation according to the difference of need, iron status and its gene polymorphism of pregnant women, to prevent the occurrence or development of gestational diabetes mellitus.

英文关键词： diabetes;gestational;iron;glucose transport protein 4;genic polymorphism;pathogenesis