Occupational exposure to particles and mitochondrial DNA - relevance for blood pressure

Abstract

BackgroundParticle 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.MethodsWe 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.ResultsWelders 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.ConclusionIncreased 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-017-0234-4) contains supplementary material, which is available to authorized users.

Reduced mitochondrial D-loop methylation levels in sporadic amyotrophic lateral sclerosis

“…In the current study, we detected an inverse correlation between D-loop methylation levels and the mtDNA copy number, an observation that has been repeatedly reported in the literature [16]. Indeed, a significant inverse correlation between D-loop methylation levels and the copy number of the mtDNA has been observed in human and mouse cell cultures [32,33], in human peripheral blood cells [23,[34][35][36][37], in colorectal cancer tissues [38], and in the human placenta [39]. Data obtained in the current study are in agreement with those studies, further suggesting that variations in Dloop methylation levels could modulate the mtDNA copy number.…”

Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity

“…MtDNA methylation levels in blood are associated with blood pressure and heart rate variability in individuals with CVD-related environmental and occupational exposures [18,19,37,40]. However, in platelets, we did not find any association between mtDNA methylation level and the most common CVD risk factors including age, BMI, blood pressure, blood glucose concentration, cholesterol, and uric acid in individuals with overweight and obesity.…”

Droplet digital PCR shows the D-Loop to be an error prone locus for mitochondrial DNA copy number determination

“…Because ACTB and GAPDH have many pseudogenes that can confound absolute mCN determination 21 , many groups use single copy number genes (e.g. RPP30 22 , APP 23 and beta globin 4 ). However, the ratio of mtDNA to a single-copy nuclear locus can saturate ddPCR duplex assays in high mCN tissues 15 .…”

“…Eukaryotic mitochondria contain a circular genome of ~16 kb encoding two rRNAs, 22 tRNAs, 13 genes for electron transport chain subunits and at least two hormone-like peptides 1 , 2 . Changes in mitochondrial DNA (mtDNA) copy number (mCN) and deletion frequency are linked to the natural aging process 3 , elevated blood pressure 4 , 5 , and diseases including cancer 6 and Alzheimer’s disease 7 . Until recently, the most precise method to quantify mCN was quantitative or real-time polymerase chain reaction (qPCR) 8 .…”