SOCS3 methylation mediated the effect of sedentary time on type 2 diabetes mellitus: the Henan Rural Cohort Study

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.