Persistent organic pollutants and plasma microRNAs: A community-based profiling analysis

Abstract

Background

Whether exposure to persistent organic pollutants (POPs) may incur microRNAs (miRNAs) dysregulation remains largely unclear.

Objectives

We aim to identify the miRNA signature and related pathways of low-level POPs exposure in a community-based population.

Methods

We used general linear regression to model the association of POPs with plasma miRNAs, adjusting for age, gender, smoking, alcohol consumption, body mass index, triglyceride, and total cholesterol levels. We performed pathway enrichment analysis based on 11 experimentally validated and prediction-based databases, and performed tissue specificity analysis.

Results

We identified 19 POPs significantly associated with 23 miRNAs at false discovery rate-adjusted P value < 0.2, most of which were related to organophosphorus and organochlorine pesticides. Pathway enrichment of the associated miRNAs highlighted chromosome segregation, RNA splicing, autophagy regulation, lipid metabolism, cell growth, development and differentiation, cell cycle regulation, neural network construction, and signal transduction. Notably, 13 POPs were positively associated with miR-6810-3p, a miRNA enriched in temporal lobe with high tissue specificity (Tissue Specificity Index = 0.78). Pathway analysis revealed that miR-6810-3p contributes to the positive regulation of autophagy and multiple cellular functions related to the nervous system such as transport along microtubules, maintenance of cell polarity, and synaptic transmission.

Conclusion

In conclusion, we identified POPs-related miRNA signatures in community-dwelling adults, and highlighted miR-6810-3p in association with multiple POPs, with a potential role in nervous system regulation.