Background

While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.

Methods

We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM_2.5, NO₂, O₃, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses.

Results

We found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM_2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease.

Conclusions

Air pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.

Background

The molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.

Objectives

To assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.

Methods

Our study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM_2.5, O₃, NO₂, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis.

Results

We found 151 significant associations between levels of PM_2.5, O₃, NO₂, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O₃, long-term exposure to PM_2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease.

Conclusion

Our results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted.