AUTHOR=He Yan , Li Yinan , Zhang Jianan , Chen Linan , Li Jing , Zhang Min , Zhang Qiu , Lu Ying , Jiang Jun , Zhang Xiaolong , Hu Jianwei , Ding Yi , Zhang Mingzhi , Peng Hao 

TITLE=FURIN Promoter Methylation Predicts the Risk of Incident Diabetes: A Prospective Analysis in the Gusu Cohort

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.873012

DOI=10.3389/fendo.2022.873012

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>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 <italic>FURIN</italic> may be involved. Here, we aimed to examine the prospective association between DNA methylation in <italic>FURIN</italic> promoter and incident diabetes during 4 years of follow-up in Chinese adults.</p></sec><sec><title>Methods</title><p>DNA methylation levels in <italic>FURIN</italic> 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 <italic>FURIN</italic> 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.</p></sec><sec><title>Results</title><p>Among the 1836 participants free of diabetes at baseline, 109 (5.94%) participants developed diabetes during the average of 4 years of follow-up. Hypermethylation at two of the eight CpG sites assayed in the <italic>FURIN</italic> promoter was associated with an increased risk of diabetes, after multivariable adjustment and multiple testing correction. Every 5% increment in methylation levels at CpG1 and CpG2 were associated with a 22% (OR=1.22, 95%CI: 1.05-1.43, <italic>P</italic>=0.009, q=0.038) and 39% (OR=1.39, 95%CI: 1.08-1.77, <italic>P</italic>=0.009, q=0.038) higher risk of incident diabetes, respectively. The gene-based association analysis revealed that DNA methylation at multiple CpG loci was jointly associated with incident diabetes (<italic>P</italic>&lt;0.001). Using the average methylation level of the 8 CpG loci in <italic>FURIN</italic> promoter revealed a similar association (OR=1.28, 95% CI: 1.02–1.62, <italic>P</italic>=0.037).</p></sec><sec><title>Conclusions</title><p>These results suggested that the hypermethylation levels in <italic>FURIN</italic> promoter were associated with an increased risk for incident diabetes in Chinese adults.</p></sec>