DNA甲基化水平及动态变化与2型糖尿病关联的前瞻性巢式病例对照研究

近年来国外不同人群的外周血DNA甲基化研究结果显示：TCF7L2、KCNQ1、SCL30A8、PTPRD、ABCG1及TXNIP基因外周血DNA甲基化可显著增加2型糖尿病的发病风险，但该6个基因甲基化与2型糖尿病的关系在我国人群中的研究尚未开展。因此，本课题拟在前期建立的大样本队列研究的基础上，采用前瞻性巢式病例对照研究设计，首先在小样本人群外周血中检测上述6个基因的启动子区甲基化水平，然后选择与2型糖尿病发病显著相关的4个候选基因，进一步在大样本巢式病例对照研究中进行验证。探讨基线和随访时各基因的甲基化水平、甲基化水平动态变化及其与环境危险因素的交互作用与2型糖尿病发病的联系，为2型糖尿病的筛检、早期诊断及干预提供前瞻性研究证据。

Recently, peripheral blood DNA methylation of TCF7L2, KCNQ1, SCL30A8, PTPRD, ABCG1 and TXNIP genes is associated with T2DM in different foreign populations, however, there is no any studies done for Chinese population in China. Based on the previously established large cohort population, the prospective nested case-control study design was used to examine the association of DNA methylation of peripheral blood leukocytes and its dynamic changing and T2DM. DNA methylation of the above mentioned 6 genes were screened with smaller sample first, and then 4 with stronger association were studied further with larger sample. The aims of our study are to explore the association between DNA methylation and its dynamic changing and T2DM, as well as the interaction between DNA methylation and environmental risk factors. The findings of this study will provide longitudinal evidence for T2DM screening, early diagnosis, and intervention.