大量研究已评估了大气细颗粒物（PM2.5）暴露与血压的关系，但其与遗传因素的交互效应对血压的影响尚不清楚。我们的前期研究发现5,10-亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性可显著增加高血压患病风险，且另有证据表明该基因多态性和PM2.5均可导致DNA甲基化异常。因此本项目拟从DNA甲基化角度探讨PM2.5和C677T基因多态性交互作用影响血压的相关机制。筛选54名健康大学生（677CC、CT和TT基因型各18人）作为研究对象，在夏、冬季2个研究周期对人群PM2.5暴露浓度及其组分和来源进行8次追踪测量，同时收集血样，检测全基因组及高血压相关特定基因DNA甲基化等生物学效应指标。综合评价PM2.5和C677T基因多态性交互作用对血压的影响，DNA甲基化修饰可能的中介效应，以及不同PM2.5成分和来源的效应差异。研究将为大气污染防控和人群心血管健康保护提供理论依据。

Numerous studies have examined the relationship between exposure to ambient fine particulate matter (PM2.5) and blood pressure; however, the interactive effects of PM2.5 with genetic factors on blood pressure were not fully understood. Our previous studies found that the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was associated an increased risk of hypertension. Considerable evidence has also documented that both MTHFR C677T polymorphism and PM2.5 exposure are associated with aberrant DNA methylation. Therefore, the aim of this project is to explore the mediating role of DNA methylaiton on the interactive effect of PM2.5 exposure and the MTHFR C677T polymorphism on blood pressure. A total of 54 healthy college students (3 types of genotype: CC, CT, and TT; 18 participants per genotype) will be recruited. The participants will be followed up for 8 times in winter and summer, undergoing standardized assessments in terms of PM2.5 exposure levels, its chemical constituents and sources, and the methylation levels of global DNA and hypertension related specific genes, etc. We propose to comprehensively 1) evaluate the interactive effect of PM2.5 exposure and MTHFR C677T polymorphism on blood pressure; 2) explore whether DNA methylation mediates the pro-hypertensive effect of the PM2.5-MTHFR interaction; and 3) examine the relationships of the variety in chemical constituents and sources of PM2.5 with blood pressure and DNA methylation. Findings from this study will provide theoretical evidence for developing strategies relating to air pollution control and cardiovascular health care.