Association Of Personal PM2.5 Exposure With Global DNA Methylation Levels

Atmospheric particulate matter pollution has become one of the most important public health issues.In terms of Global Burden of Disease(GBD)Study 2013,atmospheric particulate matter pollution accounted for 2.9 million deaths and 69.7 million disability-adjusted life-years(DALY)in the year 2013.The health effects of atmospheric particulate matter depend on its size and chemical composition.Particulate matter with an aerodynamic diameter of ?2.5 ?m(PM2.5)becomes the research focus in the field of particulate matter-related health outcomes,owing to its small size and complex chemical composition.An increasing number of epidemiological studies suggested exposure to this fine particulate matter could contributeto an increased risk of respiratory and cardiovascular illnesses and be a risk factor for lung cancer.Recent studies have suggested that PM2.5 could induce the change of global DNA methylation and thus be involved in the adverse biological effects.DNA methylation involves the addition of a methyl group to the carbon 5 position of cytosine and thus forms 5-methylcytosine,which is sensitive to environmental exposures,plays a crucial role in mediating gene expression,chromatin structure and genome stability and links the environmental exposure with human diseases.Several studies have investigated the association of PM2.5 exposure with global DNA methylation.However,these studies have reported inconsistent results,owing to the different exposure measurements and the complex chemical compositions.The majority of these published works have been conducted by utilizing fixed measurement stations assess the exposure rather than personal exposure measurements,which could possibly lead to misclassification of the exposure.To elucidate the possible mechanism of the PM2.5 or its bound polycyclic aromatic hydrocarbons(PAHs)induced global DNA methylation change,we examine the effects of personal PM2.5 exposure and PM2.5-bound PAHs on global DNA methylation in healthy Chinese cohorts and further to explore the role of plasma metabolites and genetic variants in the altered DNA methylation patterns.In the current study,a total of 307 subjects were recruited from three independent cohorts(110 from the Zhuhai cohort,118 from the Wuhan cohort and 79 from the Tianjin cohort)in southern,central and northern China,respectively,with different PM2.5 exposure levels.To evaluate the association of personal PM2.5 exposure with global DNA methylation,we measured average personal PM2.5 exposure levels using a PM2.5 sampler and a Gilian5000 pump and detected the global DNA methylation levels from peripheral blood leucocyte by an ELISA-like kit.Using gas chromatographic mass spectrometry and liquid chromatography in tandem with mass spectrometry,we detected personal PM2.5-bound PAHs components and plasma metabolic profiles,respectively,in the Tianjin cohort to analyze the relationship between the PM2.5-bound PAHs components and global DNA methylation and the mediation role of plasma metabolite.Furthermore,we explored the role of genetic variants involved in candidate metabolic enzymes in PM2.5-induced changes in DNA methylation by using the expression of quantitative trait loci(eQTL)in whole blood from Genotype-Tissue Expression(GTEx)(http://www.gtexportal.org/)and the Illumina Human Exome BeadChip.Using multiple linear regression,we identified that global DNA methylation levels were significantly correlated with PM2.5 exposure in all participants without heterogeneity(? = 0.0017,P = 0.0005)as well as in the Tianjin cohort(? = 0.0019,P=0.0008).One of the PAH components,dibenzo(a,h)anthracene(DBa),was significantly associated with 5 mC(? = 0.2163,P = 0.0003)and the plasma taurine levels(? = 0.2630,P = 3.1896×10-5).Mediation analysis showed that taurine might act as a partial mediator in the relationship between DBa and 5mC levels(P Sobel =0.0416).Moreover,we identified that rs2070457 was an expression of quantitative trait locus(eQTL)of GGT1,and this locus might be an important genetic determinant of taurine-mediated global DNA hypermethylation(p meta=-0.4264,P meta = 6.4169 ×10-5).In summary,we firstly identified that personal exposure to PM2.5 is positively related to global DNA methylation through the population-based multi-center study in healthy Chinese cohorts.Interestingly,we found that the level of plasma taurine acts as a partial mediator in the relationship between personal DBa exposure and DBa-related global hypermethylation.The global DNA methylation levels may be regulated by rs2070457 through the GGT1 expression associated with taurine metabolism.Our findings provide a new mechanism of PM2.5-related health effect and a new perspective on the disease prevention and control strategy research.