SOCS3 methylation mediated the effect of sedentary time on type 2 diabetes mellitus: The Henan Rural Cohort study
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
Authors: Liu, Xiaotian; Qian, Xinling; Tu, Runqi; Mao, Zhenxing; Huo, Wenqian; Zhang, Haiqing; Jiang, Jingjing; Zhang, Xia; Tian, Zhongyan; Li, Yuqian; Wang, Chongjian
Abstract
Background and aims: To assess the associations of sedentary time, suppressor of cytokine signaling (SOCS)-3 DNA methylation with type 2 diabetes mellitus (T2DM), and further identify the role of SOCS3 methylation in mediating the association of sedentary time with T2DM in a Chinese rural population. Methods and results: A case-control study including 1032 participants from the Henan Rural Cohort study was conducted. Restricted cubic spline analysis and logistic regression model were performed to evaluate the associations between sedentary time, SOCS3 methylation and T2DM. The mediation effect of SOCS3 methylation on the association between sedentary time and T2DM was assessed. Sensitivity analysis was conducted by excluding individuals with diagnosed T2DM. Linear dose-response relationships were found between sedentary time, methylation level of Chr17:76356190 (one novel site on SOCS3) and T2DM. Compared with the first quartile (less than 5 h/d) of sedentary time, the adjusted odds ratio (OR, 95% confidence interval, 95%CI) for those in the third (7-10 h/d) and fourth (>= 10 h/d) quartiles were 1.87 (1.22-2.85) and 3.54 (2.14-5.85), respectively. Participants in the fourth quartile of methylation level of Chr17:76356190 had lower risk of T2DM than those in the first quartile (OR (95%CI): 0.23 (0.14-0.38)). Mediation analysis showed 9.66% (6.38%-14.80%) of the association between sedentary time and T2DM was attributable to Chr17:76356190. The comparable effect estimates were observed between sedentary time, methylation level of Chr17:76356190 and undiagnosed T2DM. Conclusion: Sedentary time and methylation level of Chr17:76356190 were both independently associated with T2DM in the Chinese rural population. Furthermore, Chr17:76356190 appeared to partially mediate the effect of sedentary time on T2DM. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
AlteredSOCS3DNA methylation within exon 2 is associated with increased mRNA expression in visceral adipose tissue in gestational diabetes
EPIGENETICS
Authors: Rancourt, Rebecca C.; Ott, Raffael; Schellong, Karen; Ziska, Thomas; Melchior, Kerstin; Henrich, Wolfgang; Plagemann, Andreas
Abstract
Overweight/obesity is the main risk factor for gestational diabetes mellitus (GDM). In our cohort of pregnant women with GDM, n = 19, and without, n = 22, we previously reported a significant increase inSOCS3mRNA expression (+62%) in visceral adipose tissue (VAT) according to GDM, without altered promoter DNA-methylation. Here, we examined methylation status of additionalSOCS3exon 2 regions in VAT and maternal blood. We found significantly altered methylation at specific CpG sites corresponding to aberrant mRNA expression levels ofSOCS3in VAT. We propose a potential regulatory element/region within exon 2; however, this region does not appear to be a good blood-marker representing VAT.