Altered DNA Hydroxymethylation and Methylation and High Particulate Matter Exposure in Beijing, China

Abstract

Background: DNA methylation has been widely proposed as an epigenetic mediator of the effects of Particulate Matter (PM) exposure on human health. 5-hydroxymethylcytosine (5hmC), generated by oxidation of standard DNA methylation (5-methylcytosine, 5mC), has emerged as a novel epigenomic mark. 5hmC is both an intermediate for de-methylation and an active epigenetic mark that increases gene expression. Oxidant exposures such as PM may increase 5hmC, but effects in humans have not yet been evaluated. Methods: The Beijing Truck Driver Air Pollution Study included 60 office workers (OW) and 60 truck drivers (TD) examined on two workdays. Ambient PM10 was averaged from 27 Beijing monitors. Personal PM2.5 and Elemental Carbon (EC) were measured by portable monitors. We measured blood DNA global 5mC and 5hmC by ELISA. We fitted mixed-effects models adjusted for multiple confounders. Results: Ambient PM10 on the examination days was associated with increased global 5hmC in TD (β=0.012, 95% CI 0.004-0.021), and all participants (β=0.009, 95% CI 0.003- 0.015). Average ambient PM10 on days 4, 7, and 14 before the examinations was positively associated with global 5hmC in OW and all participants (p<0.05). 5hmC was also positively associated with personal PM2.5 in OW (β=0.012, 95% CI 0.001-0.023), TD (β=0.012, 95% CI 0.002-0.022), and all participants (β=0.008, 95% CI 0.001-0.015). In contrast, global 5mC levels were associated among OW with personal EC (β=0.564, 95% CI 0.058-1.070), and marginally with personal PM2.5 (β=0.401, 95% CI 0.004-0.798). Conclusion: 5hmC and 5mC showed different patterns of association with PM measures and time windows. 5hmC may reflect epigenetic information not captured in 5mC.