FURIN promoter methylation predicts the risk of incident diabetes: A prospective analysis in the Gusu cohort

Background: Furin has been associated with diabetes but the underlying mechanisms are unclear. As a mediator linking fixed genome and dynamic environment, DNA methylation of its coding gene FURIN may be involved. Here, we aimed to examine the prospective association between DNA methylation in FURIN promoter and incident diabetes during 4 years of follow-up in Chinese adults.
Methods: DNA methylation levels in FURIN promoter were quantified by target bisulfite sequencing using peripheral blood from 1836 participants in the Gusu cohort who were free of diabetes at baseline. To examine the association between DNA methylation levels in FURIN promoter and incident diabetes, we constructed a logistic regression model adjusting for the conventional factors. Multiple testing was controlled by adjusting for the total number of CpG sites assayed using the false-discovery rate approach.
Results: Among the 1836 participants free of diabetes at baseline, 109 (5.94%) participants developed diabetes d...

研究背景：弗林蛋白酶（Furin）与糖尿病存在相关性，但其潜在分子机制尚不明确。作为连接固定基因组与动态环境的介导因子，其编码基因FURIN的DNA甲基化（DNA methylation）或参与了该病理过程。本研究旨在探讨中国成人人群中，FURIN基因启动子区域的DNA甲基化水平与4年随访期间新发糖尿病之间的前瞻性关联。
研究方法：本研究纳入姑苏队列（Gusu cohort）中1836名基线无糖尿病的参与者，采集其外周血样本，通过靶向亚硫酸氢盐测序技术定量检测FURIN基因启动子区域的DNA甲基化水平。为明确FURIN基因启动子区域DNA甲基化水平与新发糖尿病的关联，我们构建了校正传统危险因素的logistic回归模型。采用基于检测CpG位点总数的错误发现率（false-discovery rate）法对多重检验进行校正。
研究结果：在1836名基线无糖尿病的参与者中，共有109名（占比5.94%）在随访期间新发糖尿病……