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Multiple metals exposure and blood mitochondrial DNA copy number: A cross-sectional study from the Dongfeng-Tongji
Ming Fu1, Chenming Wang1, Shiru Hong1
1Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Objective:
Mitochondria are essential organelles that execute fundamental biological processes, while mitochondrial DNA is vulnerable to environmental insults. The aim of this study was to investigate the individual and mixture effect of plasma metals on blood mitochondria DNA copy number (mtDNAcn).
Methods:
This study involved 1399 randomly selected subcohort participants from the Dongfeng-Tongji cohort. The blood mtDNAcn and plasma levels of 23 metals were determined by using quantitative real-time polymerase chain reaction (qPCR) and inductively coupled plasma mass spectrometer (ICP-MS), respectively. The multiple linear regression was used to explore the association between each metal and mtDNAcn, and the LASSO penalized regression was performed to select the most significant metals. We also used the quantile g-computation analysis to assess the mixture effect of multiple metals.
Results:
Based on multiple linear regression models, each 1% increase in plasma concentration of copper (Cu), rubidium (Rb), and titanium (Ti) was associated with a separate 0.16% [β(95% CI) = 0.158 (0.066, 0.249), P = 0.001], 0.20% [β(95% CI) = 0.196 (0.073, 0.318), P = 0.002], and 0.25% [β(95% CI) = 0.245 (0.081, 0.409), P = 0.003] increase in blood mtDNAcn. The LASSO regression also confirmed Cu, Rb, and Ti as significant predictors for mtDNAcn. There was a significant mixture effect of multiple metals on increasing mtDNAcn among the elder participants (aged ≥65), with an approximately 11% increase in mtDNAcn for each quartile increase in all metal concentrations [β(95% CI) = 0.146 (0.048, 0.243), P = 0.004].
Conclusions:
Our results show that plasma Cu, Rb and Ti were associated with increased blood mtDNA, and we further revealed a significant mixture effect of all metals on mtDNAcn among elder population. These findings may provide a novel perspective on the effect of metals on mitochondrial dysfunction.
Insights
Plasma copper, rubidium, and titanium are linked to higher blood mitochondrial DNA copy number (mtDNAcn). A mixture of metals significantly increases mtDNAcn in older adults, suggesting a role in mitochondrial dysfunction.
Area of Science:
- Environmental Health
- Molecular Biology
- Toxicology
Background:
- Mitochondria are vital organelles, but their DNA (mtDNA) is susceptible to environmental damage.
- Mitochondrial DNA copy number (mtDNAcn) is a biomarker for mitochondrial function and health.
- Metals are ubiquitous environmental factors with potential toxicological effects.
Purpose of the Study:
- To investigate the individual effects of plasma metals on blood mtDNAcn.
- To examine the combined (mixture) effect of multiple plasma metals on blood mtDNAcn.
- To explore associations between specific metals and mtDNAcn in a large cohort.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) for blood mtDNAcn.
- Inductively coupled plasma mass spectrometry (ICP-MS) for plasma metal levels (23 metals).
- Multiple linear regression, LASSO penalized regression, and quantile g-computation for statistical analysis.
Main Results:
- Plasma copper (Cu), rubidium (Rb), and titanium (Ti) were individually associated with increased blood mtDNAcn.
- LASSO regression identified Cu, Rb, and Ti as significant predictors of mtDNAcn.
- A significant mixture effect of metals was observed, increasing mtDNAcn in elder participants (≥65 years).
Conclusions:
- Elevated plasma levels of Cu, Rb, and Ti correlate with increased blood mtDNAcn.
- The combined exposure to multiple metals has a notable impact on mtDNAcn, particularly in the elderly.
- These findings offer insights into metal-induced mitochondrial dysfunction and potential biomarkers.
