Renjie Chen1, Xia Meng2, Ang Zhao3, Cuicui Wang3, Changyuan Yang3, Huichu Li3, Jing Cai4, Zhuohui Zhao4, Haidong Kan5. 1. 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. 2. Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta 30322, GA, USA. 3. School of Public Health, Key Lab of Public Health Safety of the Ministry of Education, Fudan University, Shanghai 200032, China. 4. 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. 5. 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.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: Rossella Alfano; Zdenko Herceg; Tim S Nawrot; Marc Chadeau-Hyam; Akram Ghantous; Michelle Plusquin Journal: Curr Environ Health Rep Date: 2018-12
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