F2RL3基因甲基化在PM2.5暴露对凝血功能影响中的调节作用

Epidemiological studies have shown that PM2.5 exposure can have effects on blood coagulation. However, the biological mechanisms remain to be investigated. Platelets and thrombin have close relationship with blood coagulation. Proteinase-activated receptor 4 (PAR4) plays an important role in platelet aggregation as the thrombin receptor. This study will explore the related mechanisms on how PM2.5 exposure influences blood coagulation from the perspective of methylation of F2RL3 gene which encodes for PAR4. We will recruit 60 bus drivers as the PM2.5 exposure group, and 60 office workers as the control group. The two study groups’ exposure concentrations of PM2.5 and its chemical compositions will be measured continuously in the three study periods of winter, spring and summer. Furthermore, peripheral venous blood will be extracted from the study population each time in the three study periods, in total three times to be carried out, in order to follow up the variations of F2RL3 gene methylation, expression level of PAR4, and levels of blood coagulation biomarkers. In combination of biological significance of these indicators, the regulation effects of F2RL3 gene methylation on the influence of PM2.5 exposure on blood coagulation will be analyzed and discussed. The study will not only explore the mechanisms of different concentrations and various compositions of PM2.5 exposure on blood coagulation, but also screen the early biomarkers in this process. The results will provide scientific evidence for PM2.5 pollution control and cardiovascular health protection in public health.

流行病学研究显示PM2.5暴露可对凝血功能产生影响，但是生物学机制仍有待探讨。血小板和凝血酶与凝血功能密切相关，PAR4作为凝血酶受体与凝血酶结合后，在血小板聚集中起着重要作用。本项目拟从PAR4的编码基因（F2RL3）甲基化角度出发，探讨PM2.5暴露对凝血功能影响的相关机制。招募60名公交车司机作为PM2.5暴露组，60名办公室职员作为对照组。在冬季、春季、夏季3个研究时期对两组人群的PM2.5暴露浓度和化学组分进行连续测量，并在每个时期采集外周静脉血1次，共采集3次，用于F2RL3基因甲基化、PAR4和凝血功能指标的追踪测定。结合测定指标的生物学意义，分析F2RL3基因甲基化在PM2.5对凝血功能影响中的调节作用。研究结果不仅能探索PM2.5不同浓度及组分对凝血功能影响的相关机制，还能筛选PM2.5对凝血功能影响的早期生物标志物，为PM2.5污染控制和人群心血管健康保护提供科学依据。

流行病学研究显示PM2.5暴露可对人体凝血功能产生影响，但是其中的生物学机制尚不清楚。本研究拟从凝血酶受体基因甲基化的角度出发，探讨PM2.5暴露对凝血功能影响的相关生物学机制。研究中招募了31名出租司机作为PM2.5暴露组，和33名办公室职员作为对照组。在冬季、春季、夏季对两组研究人群进行3个时期的连续追踪调查。连续测定研究人群在3个时期的PM2.5暴露水平及组分，并在3个时期分别采集研究对象的外周静脉血1次，用于F2RL3基因甲基化水平和凝血功能相关指标的测定。结果显示个体PM2.5暴露与F2RL3中CpG_4甲基化水平降低间存在显著关联，并且个体PM2.5暴露与凝血功能指标sP-selectin水平升高存在显著关联，个体PM2.5浓度每升高一个IQR(71.27 μg/m3)，sP-selectin水平变化百分比为13.66%（95%CI: 7.75%, 19.57%)。提示F2RL3中CpG_4甲基化水平的降低可能在PM2.5暴露导致凝血功能影响中起到了重要的调节作用。