CDKN2A基因在胰岛β细胞衰老致2型糖尿病的机制及其致病变异定位

胰岛β细胞的衰老是导致2型糖尿病（T2D）发生的关键因素之一。课题组前期在9年随访的队列人群中开展遗传学研究发现，衰老相关基因CDKN2A基因区域存在影响T2D发生及胰岛β细胞功能动态变化的位点。本项目拟在此基础上，通过对CDKN2A基因区域开展深度测序，结合大样本病例-对照人群验证发现该区域中影响中国人T2D的致病变异；通过对不同基因型者的胰岛β细胞开展转录组测序，结合体外细胞和分子生物学实验，阐明CDKN2A基因及重要变异调控衰老通路、参与T2D发生的内在机制，为了解衰老过程中胰岛β细胞功能调控的机制奠定基础。

Pancreatic β cell senescence is a key factor of type 2 diabetes in Chinese. Previously, we identified senescence-associated gene CDKN2A as a susceptible T2D loci and could influence β cell function in a 9-year perspective cohort in Chinese. Based on this, we plan to perform deep sequencing in CDKN2A gene region to detect potential casual variants and RNA-seq to obtain different transcriptome profiles. Moreover, we will elucidate the mechanism of how CDKN2A and its casual variants regulate the senescence pathway and participate T2D development. Our research is of importance to know the dynamic changes of β cells in the process of cell senescence.