title: Effects of particulate matter exposure on blood 5-hydroxymethylation: results from the Beijing truck driver air pollution study.
abstract: Previous studies have reported epigenetic changes induced by environmental exposures. However, previous investigations did not distinguish 5-methylcytosine (5mC) from a similar oxidative form with opposite functions, 5-hydroxymethylcytosine (5hmC). Here, we measured blood DNA global 5mC and 5hmC by ELISA and used adjusted mixed-effects regression models to evaluate the effects of ambient PM10 and personal PM2.5 and its elemental components-black carbon (BC), aluminum (Al), calcium (Ca), potassium (K), iron (Fe), sulfur (S), silicon (Si), titanium (Ti), and zinc (Zn)-on blood global 5mC and 5hmC levels. The study was conducted in 60 truck drivers and 60 office workers in Beijing, China from The Beijing Truck Driver Air Pollution Study at 2 exams separated by one to 2 weeks. Blood 5hmC level (0.08%) was ∼83-fold lower than 5mC (6.61%). An inter-quartile range (IQR) increase in same-day PM10 was associated with increases in 5hmC of 26.1% in office workers (P = 0.004), 20.2% in truck drivers (P = 0.014), and 21.9% in all participants combined (P < 0.001). PM10 effects on 5hmC were increasingly stronger when averaged over 4, 7, and 14 d preceding assessment (up to 132.6% for the 14-d average in all participants, P < 0.001). PM10 effects were also significant after controlling for multiple testing (family-wise error rate; FWER < 0.05). 5hmC was not correlated with personal measures of PM2.5 and elemental components (FWER > 0.05). 5mC showed no correlations with PM10, PM2.5, and elemental components measures (FWER > 0.05). Our study suggests that exposure to ambient PM10 affects 5hmC over time, but not 5mC. This finding demonstrates the need to differentiate 5hmC and 5mC in environmental studies of DNA methylation.
authors.affiliation: a Department of Environmental Health; Harvard T.H. Chan School of Public Health ; Boston , MA , USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Sanchez-Guerra
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Citlalli
authors.initials: C
authors.lastname: Osorio-Yanez
authors.forename: Jia
authors.initials: J
authors.lastname: Zhong
authors.forename: Yana
authors.initials: Y
authors.lastname: Chervona
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Dou
authors.initials: D
authors.lastname: Chang
authors.forename: John P
authors.initials: JP
authors.lastname: McCracken
authors.forename: Anaite
authors.initials: A
authors.lastname: Díaz
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.forename: Choong-Min
authors.initials: CM
authors.lastname: Kang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D044503:5-Methylcytosine / Q000097:blood / Q000031:analogs & derivatives; D000293:Adolescent; D000328:Adult; D000397:Air Pollution / Q000009:adverse effects*; D000068476:Beijing; D003596:Cytosine / Q000031:analogs & derivatives* / Q000097:blood; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D055815:Young Adult
chemical_list: D052638:Particulate Matter; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 10 μm; 2.5 μm; 5-hydroxymethylcytosine; 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine; 5mC, 5-methylcytosine; Al, aluminum; BC, black carbon; BMI, body mass index; CI, confidence interval; Ca, calcium; DNA methylation; ELISA, enzyme-linked immunosorbent assay; Epigenetics; FWER, family-wise error rate; Fe, iron; HPLC, high-performance liquid chromatography; K, potassium; PM, particulate matter; PM10, particulate matter ≤; PM2.5, particulate matter ≤; Particulate Matter; S, sulfur; Si: silicon; TET, ten-eleven translocation enzymes; Ti, titanium and Zn: zinc.