循环microRNA与2型糖尿病关联的前瞻性研究

Type 2 diabetes mellitus (T2DM) is one kind of polygenic heterogeneous disease which has complicated genetic background. MicroRNA (miRNA) is the upstream key factor for regulating gene expression. The amount of the upstream miRNAs is a lot less than that of the downstream vast target genes. Although more and more researches indicated that circulating miRNAs which exist in human blood were closely related with T2DM, it lacks perspective study of large-scale cohort population. From the field survey to the laboratory and from the population to the upstream miRNA regulating gene expression, this project will research the genetic factor of T2DM by Meta analysis, nested case-control study based on cohort population and modern molecular biological technique, to clarify the epidemic dynamics of T2DM in Gannan Hakka population, to find the circulating miRNAs related to T2DM, to ascertain the correlation between the circulating miRNAs and T2DM, and to explore the interaction between the circulating miRNAs and the environmental factors. It aimed at searching the pathogenic clues of T2DM, establishing the theoretical basis for ultimately revealing the its pathogenesis and mechanism, and offering the scientific evidence for implementing the hygienic policy and preventive health-care measures in the future.

2型糖尿病（type 2 diabetes mellitus，T2DM）是遗传背景十分复杂的多基因异质性疾病。MicroRNA（miRNA）是调控基因表达的上游的关键因素，与海量的下游靶基因相比，起调控作用的上游miRNA的数量要少很多。越来越多的研究表明，存在于人血液中的循环miRNA与T2DM密切相关，但尚缺乏大样本队列人群的前瞻性研究证实。本项目拟通过Meta分析和以队列人群为基础的巢式病例对照研究方法，结合现代分子生物学技术，从现场到实验室，从群体到调控基因表达的上游miRNA研究T2DM的遗传因素，弄清赣南客家人群T2DM的发病动态，寻找T2DM相关的循环miRNA，明确循环miRNA与T2DM的关联，探讨miRNA与环境因素在T2DM发病中的交互作用。旨在寻找T2DM的病因线索，为最终揭示其病因和发病机理奠定理论基础，为今后卫生决策和预防保健措施的贯彻执行提供科学依据。

2型糖尿病（type 2 diabetes mellitus，T2DM）是遗传背景十分复杂的多基因异质性疾病。T2DM的发病率、患病率、致残率和病死率仍然居高不下，如何早期发现和早期预防T2DM已成为全球急需解决的重要公共卫生问题。本项目在赣南地区建立了T2DM队列人群，开展T2DM流行病学现况调查及随访，描述T2DM发病现状及分布特征，分析赣南地区T2DM的发病动态；分析T2DM与环境因素之间的关联及其关联程度；分析循环miRNA与T2DM遗传易感性及疾病表型之间的关联及其关联程度。主要结果：① 建立了T2DM队列人群， 2017-2020年期间，非患者队列共检出T2DM新发病例63人，发病率3.11%，发病密度3.71%；② 分析了T2DM与环境因素之间的关联及其关联程度，寻找出T2DM的危险因素和保护因素。③ T2DM病例组与对照组血清外泌体miRNA表达比较，38个miRNA表达差异具有高度显著性（P<0.01），71个miRNA表达差异具有显著性（0.01≤P<0.05）。本项目弄清了赣南地区T2DM的发病动态，寻找出T2DM的病因线索，为最终揭示其病因和发病机理奠定理论基础，为赣南地区今后卫生决策和制定适宜的群体干预措施提供了科学依据。