ABCA1/G1去甲基化介导PM2.5暴露致学龄儿童低脂蛋白血症的机制研究

PM2.5暴露与儿童低脂蛋白血症发病风险的关联引起关注，但早期损害机制不明。本项目围绕PM2.5暴露可引起DNA甲基稳态“平衡受扰”这一表观遗传起始分子事件，提出胆固醇逆向转运基因ABCA1/G1去甲基化是PM2.5暴露致学龄儿童低脂蛋白血症潜在机制的研究假设。本项目拟采用多中心（深圳、石家庄、佳木斯）学龄儿童定群随访（2年4次随访）结合环境表观遗传毒性细胞实验研究设计，使用实时在线数据及大气国控站数据计算儿童实际场景PM2.5综合暴露，利用SiRNA转染沉默基因表达，拟阐明PM2.5综合暴露与HDL-C及ABCA1/G1去甲基化水平之间的剂量—效应关系以及ABCA1/G1去甲基化与低脂蛋白血症之间的响应关系，揭示ABCA1/G1去甲基化介导PM2.5暴露致学龄儿童低脂蛋白血症的机制。本研究可以深入了解PM2.5暴露对儿童血脂异常损伤的表观遗传机制，为儿童低脂蛋白血症防控提供新依据。

The potential hypoalphalipoproteinemia effect of PM2.5 exposure for school-aged children has raised concern, however, the underlying molecular mechanism remains unclear. This project will focus on DNA demethylation caused by PM2.5 exposure that was considered as one of the epigenetic initiation molecular events. We hypothesize that ABCA1/G1 demethylation inducing-decreased HDL-C levels are the potential biological mechanism of PM2.5 exposure-caused hypolipoproteinemia in school-age children. A multi-center school-age children follow-up study combined with in vitro environmental epigenetic toxicity experiment will be carried out. The comprehensive exposure levels of M2.5 school-age children were calculated in multi-center via a combination of real-time online monitoring equipment and a national atmospheric monitoring station. We will clarify the dose-effect relationship among PM2.5 comprehensive exposure, the level of HDL-C, and ABCA1/G1 demethylation, and further analyze the potential molecular mechanism of hypolipoproteinemia in response to ABCA1/G1 demethylation. This project will reveal the potential relationship between the demethylation of ABCA1/G1 gene and PM2.5 exposure-caused hypoalphalipoproteinemia in school-age children. This study will provide new insights on understanding the epigenetic mechanism effect of PM2.5 exposure on dyslipidemia, which contributes to the prevention and control of school-age children’s hypolipoproteinemia.