title: DNA hypomethylation and its mediation in the effects of fine particulate air pollution on cardiovascular biomarkers: A randomized crossover trial.
abstract: Short-term exposure to fine particulate matter (PM2.5) air pollution has been associated with altered DNA methylation in observational studies, but it remains unclear whether this change mediates the effects on cardiovascular biomarkers.
  
  
  
  To examine the impact of ambient PM2.5 on gene-specific DNA methylation and its potential mediation in the acute effects of PM2.5 on cardiovascular biomarkers.
  
  
  
  We designed a randomized, double-blind crossover trial using true or sham air purifiers for 48h among 35 healthy college students in Shanghai, China, in 2014. We measured blood global methylation estimated in long interspersed nucleotide element-1 (LINE‑1) and Alu repetitive elements, methylation in ten specific genes, and ten cardiovascular biomarkers. We used linear mixed-effect models to examine the associations between PM2.5 and methylation. We also performed causal mediation analyses to evaluate the potential mediation of methylation in the associations between PM2.5 and biomarkers.
  
  
  
  Air purification increased DNA methylation in repetitive elements and all candidate genes. An IQR increase (64μg/m(3)) in PM2.5 was significantly associated with reduction of methylation in LINE-1 (1.44%), one pro-inflammatory gene (CD40LG, 9.13%), two pro-coagulant genes (F3, 15.20%; SERPINE1, 3.69%), and two pro-vasoconstriction genes (ACE, 4.64%; EDN1, 9.74%). There was a significant mediated effect (17.82%, P=0.03) of PM2.5 on sCD40L protein through CD40LG hypomethylation. Hypomethylation in other candidate genes generally showed positive but non-significant mediation.
  
  
  
  This intervention study provided robust human evidence that ambient PM2.5 could induce rapid decreases in DNA methylation and consequently partly mediate its effects on cardiovascular biomarkers.
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China; Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Fudan University, Shanghai 200032, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta 30322, GA, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Zhao
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China.
authors.forename: Huichu
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China; Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China; Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China.
authors.forename: Zhuohui
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China; Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Fudan University, Shanghai 200032, China. Electronic address: kanh@fudan.edu.cn.
authors.forename: Haidong
authors.initials: H
authors.lastname: Kan
mesh_terms: D061808:Air Filters; D015415:Biomarkers / Q000032:analysis*; D002681:China; D018592:Cross-Over Studies; D019175:DNA Methylation / Q000235:genetics*; D004311:Double-Blind Method; D004781:Environmental Exposure / Q000032:analysis*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D052638:Particulate Matter / Q000032:analysis*
chemical_list: D015415:Biomarkers; D052638:Particulate Matter
keywords: Air pollution; Cardiovascular biomarker; DNA methylation; Fine particulate matter; Mediation; Randomized controlled trial