Associations of selenium exposure with blood lipids: Exploring mediating DNA methylation sites in general Chinese urban non-smokers

Selenium (Se) is widely distributed in the total environment and people are commonly exposed to Se, while the potential effects and mechanisms of Se exposure on blood lipids have not been well established. This study aimed to assess the associations of urinary Se (Se\\U) with blood lipids and explore the potential mediating DNA methylation sites. We included 2844 non-smoke participants from the second follow-up (2017-2018) of the Wuhan-Zhuhai cohort (WHZH) in this study. Se\\U and blood lipids [i.e., total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and highdensity lipoprotein cholesterol (HDL)] for all participants were determined. The associations of Se\\U with blood lipids were analyzed by generalized linear models. Then, we conducted the blood lipids related epigenome-wide association studies (EWAS) among 221 never smokers, and the mediation analysis was conducted to explore the potential mediating cytosine-phosphoguanine (CpG) sites in the above associations. In this study, the Se\\U concentration of the participants in this study was 1.40 (0.94, 2.08) mu g/mmol Cr. The Se\\U was positively associated with TC and LDL, and not associated with TG and HDL. We found 131, 3, and 1 new CpG sites related to TC, HDL, and LDL, respectively. Mediation analyses found that the methylation of cg06964030 (within MIR1306) and cg15824094 (within PLCH2) significantly mediated the positive association between Se\\U and TC. In conclusion, high levels of Se exposure were associated with increased TC and LDL among non-smokers, and the methylation of MIR1306 and PLCH2 partly mediated Se-associated TC increase. These findings provide new insights into the effects and mechanisms of Se exposure on lipids metabolism and highlight the importance of controlling Se exposure and intake for preventing high blood lipids.