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Published on: December 21, 2016
Polycyclic aromatic hydrocarbon exposure, miRNA genetic variations, and associated leukocyte mitochondrial DNA copy
Xiaoran Duan1, Yongli Yang2, Hui Zhang3
1Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China; Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, Henan, China.
Abstract:
Mitochondria DNA was preferentially attacked by the exogenous carcinogens including polycyclic aromatic hydrocarbons (PAHs) relative to nuclear DNA, and nuclear gene variants may account for variability in the mitochondrial DNA copy number (mtDNAcn). However, it remains unclear whether miRNA genetic variations are associated with mitochondrial DNA damage in the PAH-exposed workers. Therefore, we measured the leukocyte mtDNAcn, urinary 1-hydroxypyrene (1-OHPYR), environmental PAH exposure, and miRNA genetic polymorphisms among 544 coke oven workers and 238 healthy control participants. We found that the mtDNAcn in the exposure group (0.60 ± 0.29) was significantly lower than that in the control group (1.03 ± 0.31) (t = 18.931, P < 0.001). Spearman correlation analysis showed that the peripheral blood leukocyte mtDNAcn had significantly negative correlations with the levels of 1-OHPYR and environmental PAH exposure (P < 0.001). Covariance analysis indicated that miR-210 rs11246190 AA, miR-210 rs7395206 CC, and miR-126 rs2297538 GG probably promoted a decrease in leukocyte mtDNAcn in the exposure or control groups (P < 0.05). In generalized linear model, miR-210 rs11246190 GG was a protective factor of mtDNAcn, and environmental PAH exposure was the risk factor of the mtDNAcn. In conclusion, the decrease of leukocyte mtDNAcn is the result of a combination of environmental and genetic factors.
Insights
Polycyclic aromatic hydrocarbon (PAH) exposure significantly reduces mitochondrial DNA copy number (mtDNAcn) in coke oven workers. Specific microRNA (miRNA) genetic variations, alongside PAH exposure, influence this decrease, highlighting combined environmental and genetic factors.
Area of Science:
- Environmental Health
- Molecular Biology
- Genetics
Background:
- Mitochondrial DNA (mtDNA) is susceptible to damage from exogenous carcinogens like polycyclic aromatic hydrocarbons (PAHs).
- Variability in mitochondrial DNA copy number (mtDNAcn) may be influenced by nuclear gene variants.
- The association between microRNA (miRNA) genetic variations and mtDNA damage in PAH-exposed populations is not well understood.
Purpose of the Study:
- To investigate the relationship between miRNA genetic variations and mitochondrial DNA damage in workers exposed to PAHs.
- To assess the impact of environmental PAH exposure on leukocyte mtDNA copy number (mtDNAcn).
Main Methods:
- Measured leukocyte mtDNAcn, urinary 1-hydroxypyrene (1-OHPYR) as a biomarker of PAH exposure, and environmental PAH levels.
- Genotyped miRNA polymorphisms in 544 coke oven workers and 238 healthy controls.
- Utilized Spearman correlation and covariance analysis to examine associations.
Main Results:
- Leukocyte mtDNAcn was significantly lower in the PAH-exposed group compared to controls (0.60 ± 0.29 vs. 1.03 ± 0.31).
- mtDNAcn showed significant negative correlations with urinary 1-OHPYR and environmental PAH exposure.
- Specific miRNA polymorphisms (miR-210 rs11246190 AA, miR-210 rs7395206 CC, miR-126 rs2297538 GG) were associated with decreased mtDNAcn, while miR-210 rs11246190 GG appeared protective.
Conclusions:
- Decreased leukocyte mtDNAcn in coke oven workers results from a combination of environmental PAH exposure and specific genetic factors related to miRNA.
- Environmental PAH exposure is a risk factor for reduced mtDNAcn, while certain miRNA genotypes may offer protection.
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