大气可吸入颗粒物PM10与DGCR8基因多态性交互作用对子痫前期的影响及机制研究

大气污染物对健康的危害不仅受暴露浓度影响，还与遗传易感性相关。我们前期的研究发现大气可吸入颗粒物(PM10)、miRNAs合成通路基因DGCR8rs1640299和rs720014多态性均与PE相关，且另有证据表明两者均可影响miRNAs存在共同的致病通路，提示它们可能存在交互影响PE。因此本项目拟从miRNAs角度探讨PM10和DGCR8多态性交互作用影响PE的机制，首先在前期研究基础上继续招募对象，收集413名PE和826名对照的环境暴露资料、外周血和胎盘标本。然后通过分层分析探讨PM10暴露和DGCR8rs1640299、rs720014基因型的交互作用对PE的影响。最后检测与PM暴露相关的胎盘miR-20a，-146a，-222和-21水平，利用中介效应分析探讨胎盘miRNAs在PM10与DGCR8多态性参与PE中的作用。本研究为了解大气污染与遗传因素相互作用对PE的影响提供数据。

The health hazards of air pollutants are not only affected by exposure levels but also related to genetic susceptibility. Our previous research found that inhalable particulate matters (PM10), miRNAs machinery genes DGCR8 rs1640299, rs720014 polymorphisms are related to PE, and other previous researches had also proofed that that both of them could cause aberrant miRNAs expression and share common pathogenic pathway, suggesting that they may have interaction effects on risk of PE. Therefore, our project aimed at exploring the mechanism of PM10 and DGCR8 polymorphism interactions affecting PE from the perspective of miRNAs. Firstly, we would continue to recruit subjects based on previous research and collect environmental exposure data, peripheral blood and placental specimens. Then based on the PM10 exposure status and genotypes of DGCR8rs1640299 and rs720014 of 413 PE and 826 controls, we would analyze the effects of the interaction between the two on PE by stratified analysis. Finally, the levels of placenta miR-20a, -146a, -222, and -21 related to PM exposure would be detected, and the role of placental miRNAs in the involvement of PM10 and DGCR8 polymorphisms in PE would be analyzed using mediator analysis. This study will provide data for understanding the effects of atmospheric pollution and genetic factors on PE.