Background-The mitochondrion is the primary target of oxidative stress in response to exogenous environments. Mitochondrial DNA (mtDNA) is independent from nuclear DNA and uses separate epigenetic machinery to regulate mtDNA methylation. The mtDNA damage induced by oxidative stress can cause mitochondrial dysfunction and is implicated in human diseases; however, mtDNA methylation has been largely overlooked in environmental studies relating to human disease. The purpose of this study was to examine the association between exposure to fine metal-rich particulates (particulate matter <2.5 μm in diameter [PM2.5]) from welding in a boilermaker union and blood mtDNA methylation in relation to heart rate variability. Methods and Results-Forty-eight healthy men were recruited on multiple sampling cycles at the Boilermaker Union Local 29, located in Quincy, Massachusetts. We measured personal PM2.5 in the background ambient environment. We measured blood mtDNA methylation in the mtDNA promoter (D-loop) and genes essential for ATP synthesis (MT-TF and MT-RNR1) by bisulfite pyrosequencing. All analyses were adjusted for demographics, type of job, season, welding-work day, and mtDNA methylation experimental batch effect. The participants' PM2.5 exposure was significantly higher after a welding-work day (mean 0.38 mg/m3) than the background personal level (mean 0.15 mg/m3, P<0.001). Blood mtDNA methylation in the D-loop promoter was associated with PM2.5 levels (β=-0.99%, SE=0.41, P=0.02). MT-TF and MT-RNR1 methylation was not associated with PM2.5 exposure (β=0.10%, SE=0.45, P=0.82). Interaction of PM2.5 exposure levels and D-loop promoter methylation was significantly associated with markers of heart rate variability. Conclusions-Blood mtDNA methylation levels were negatively associated with PM2.5 exposure and modified the adverse relationships between PM2.5 exposure and heart rate variability outcomes.
Byun, H. M., Colicino, E., Trevisi, L., Fan, T., Christiani, D. C., & Baccarelli, A. A. (2016). Effects of air pollution and blood mitochondrial DNA methylation on markers of heart rate variability. Journal of the American Heart Association, 5(4). https://doi.org/10.1161/JAHA.116.003218