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Published on: July 12, 2024
Ambient particulate air pollution and microRNAs in elderly men
Serena Fossati1, Andrea Baccarelli, Antonella Zanobetti
1From the Departments of aEnvironmental Health and cEpidemiology, Harvard School of Public Health, Boston, MA; bDepartment of Biomedical and Clinical Sciences "Luigi Sacco," University of Milan, Milan, Italy; dLaboratory of Environmental Epigenetics, Department of Environmental and Occupational Health, University of Milan, Milan, Italy; eVA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA; and fGenetic Epidemiology Unit, Channing Laboratory, Brigham and Women's Hospital, Boston, MA.
Ambient particulate matter exposure downregulates microRNAs (miRNAs) linked to cardiovascular health. Genetic variations in microRNA-related genes may alter these effects.
Area of Science:
- Environmental Health
- Molecular Biology
- Cardiovascular Disease Research
Background:
- Ambient particulate matter (PM) exposure is linked to cardiovascular disease mortality and morbidity.
- MicroRNAs (miRNAs) regulate gene expression and their altered expression is implicated in cardiovascular disease processes.
- Genetic variations (polymorphisms) in miRNA-related genes may influence individual responses to PM exposure.
Purpose of the Study:
- To investigate the association between ambient particle exposure and blood leukocyte miRNA expression.
- To examine potential modification of these associations by single nucleotide polymorphisms (SNPs) in miRNA-related genes.
Main Methods:
- Analysis of 14 candidate miRNAs in 153 elderly males exposed to fine PM (PM2.5), black carbon, organic carbon, and sulfates.
- Linear regression models assessed effects of various PM time windows (4-hour to 28-day averages) and SNP-pollutant interactions.
- In silico pathway analysis identified biological pathways targeted by associated miRNAs.
Main Results:
- Exposure to PM pollutants was negatively associated with the expression of several miRNAs, including miR-1, -126, -146a, -155, -21, -222, and -9.
- Strongest associations were observed with 7-day moving averages for PM2.5 and black carbon, and 48-hour averages for organic carbon.
- Significant SNP-by-pollutant interactions were found for specific SNPs in GEMIN4 and DGCR8 genes, modifying the effects of PM on certain miRNAs.
Conclusions:
- Ambient particle exposure can lead to downregulation of specific miRNAs involved in PM-related processes.
- Polymorphisms in the GEMIN4 and DGCR8 genes may modify the association between PM exposure and miRNA expression.
