Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Environmental Health

Research

James W. MacDonald¹  Yongmei Liu²  Lindsay M. Reynolds²  Gloria C. Chi³  Mark D. Hensley³  Joel D. Kaufman⁴  Lifang Hou⁵  R. Graham Barr⁶  Kathleen M. Donohue⁶  David S. Siscovick⁷  Charles E. McCall⁸ 

[1] Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA;Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA;Department of Epidemiology, School of Public Health, University of Washington, Box 357236, 1959 NE Pacific St, 98195, Seattle, WA, USA;Department of Epidemiology, School of Public Health, University of Washington, Box 357236, 1959 NE Pacific St, 98195, Seattle, WA, USA;Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA;Department of Preventive Medicine, Division of Cancer Epidemiology and Prevention, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;Division of General Medicine, Mailman School of Public Health, Columbia University, New York, NY, USA;Division of Pulmonary, Allergy & Critical Care, Columbia University Medical Center, New York, NY, USA;New York Academy of Medicine, New York, NY, USA;Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA;

关键词: Air pollution;    PM;    NO;    ANKHD1;    LGALS2;    ANKRD11;    BAZ2B;    PPIE;    DNA methylation;   

DOI  :  10.1186/s12940-016-0202-4

 received in 2016-06-27, accepted in 2016-11-24,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55).MethodsOne-year average ambient fine particulate matter (PM2.5) and oxides of nitrogen (NOX) concentrations were predicted at participants’ (n = 1,207) addresses using spatiotemporal models. We assessed DNA methylation in circulating monocytes at 1) 2,713 CpG sites associated with mRNA expression of nearby genes and 2) probes mapping to Alu and LINE-1 repetitive elements (surrogates for global DNA methylation) using Illumina’s Infinium HumanMethylation450 BeadChip. We used linear regression models adjusted for demographics, smoking, physical activity, socioeconomic status, methyl-nutrients, and technical variables. For significant air pollution-associated methylation sites, we also assessed the association between expression of gene transcripts previously associated with these CpG sites and air pollution.ResultsAt a false discovery rate of 0.05, five candidate CpGs (cg20455854, cg07855639, cg07598385, cg17360854, and cg23599683) had methylation significantly associated with PM2.5 and none were associated with NOX. Cg20455854 had the smallest p-value for the association with PM2.5 (p = 2.77 × 10−5). mRNA expression profiles of genes near three of the PM2.5-associated CpGs (ANKHD1, LGALS2, and ANKRD11) were also significantly associated with PM2.5 exposure. Alu and LINE-1 methylation were not associated with long-term air pollution exposure.ConclusionsWe observed novel associations between long-term ambient air pollution exposure and site-specific DNA methylation, but not global DNA methylation, in purified monocytes of a multi-ethnic adult population. Epigenetic markers may provide insights into mechanisms underlying environmental factors in complex diseases like atherosclerosis.

【 授权许可】

CC BY   
© The Author(s). 2016