title: Occupational exposure to particles and mitochondrial DNA - relevance for blood pressure.
abstract: Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and cardiovascular response, measured as blood pressure.
  
  
  
  We investigated 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal sampling of the welders' exposure to respirable dust was performed during work hours (average sampling time: 6.8 h; range: 2.4-8.6 h) and blood pressure was measured once for each subject. We measured relative mtDNA copy number by quantitative PCR and methylation of the mitochondrial regulatory region D-loop and the tRNA encoding gene MT-TF by bisulfite-pyrosequencing. We calculated the relative number of unmethylated D-loop and MT-TF as markers of mtDNA function to explore the modification of mtDNA on the association between particle exposure and blood pressure. General linear models were used for statistical analyses.
  
  
  
  Welders had higher mtDNA copy number (β = 0.11, p = 0.003) and lower DNA methylation of D-loop (β = -1.4, p = 0.002) and MT-TF (β = -1.5, p = 0.004) than controls. Higher mtDNA copy number was weakly associated with higher personal respirable dust exposure among welders with exposure level above 0.7 mg/m3(β = 0.037, p = 0.054). MtDNA function modified the effect of welding fumes on blood pressure: welders with low mtDNA function had higher blood pressure than controls, while no such difference was found in the group with high mtDNA function.
  
  
  
  Increased mtDNA copy number and decreased D-loop and MT-TF methylation were associated with particle-containing welding fumes exposure, indicating exposure-related oxidative stress. The modification of mtDNA function on exposure-associated increase in blood pressure may represent a mitochondria-environment interaction.
authors.affiliation: Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden. yiyi.xu@med.lu.se.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden.
authors.forename: Huiqi
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Hedmer
authors.affiliation: Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden.
authors.forename: Mohammad Bakhtiar
authors.initials: MB
authors.lastname: Hossain
authors.affiliation: Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Tinnerberg
authors.affiliation: Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden.|Unit of Metals & Health, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Broberg
authors.affiliation: Division of Occupational and Environmental Medicine, Laboratory Medicine, Lund University, 221 85, Lund, Sweden.|Unit of Occupational Medicine, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Albin
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000009:adverse effects* / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D056915:DNA Copy Number Variations / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000235:genetics; D004391:Dust / Q000032:analysis*; D004784:Environmental Monitoring; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D013548:Sweden; D014896:Welding; D055815:Young Adult
chemical_list: D000395:Air Pollutants, Occupational; D004272:DNA, Mitochondrial; D004391:Dust
keywords: Blood pressure; Copy number; DNA methylation; Mitochondria; Particle