Associations Between Genome-wide Gene Expression and Ambient Nitrogen Oxides

Area of Science:

• Environmental Health
• Genomics
• Molecular Biology

Background:

• Ambient air pollution exposure is a growing public health concern.
• Biological perturbations from environmental exposures may manifest in molecular changes.
• Gene expression in peripheral blood mononuclear cells (PBMCs) can serve as a biomarker for such perturbations.

Purpose of the Study:

• To investigate the association between long-term exposure to ambient air pollution, specifically nitrogen oxides (NOx), and genome-wide gene expression levels in PBMCs.
• To explore potential overlaps between gene expression changes induced by air pollution and those associated with cigarette smoking.
• To examine the relationship between NOx exposure and DNA methylation patterns.

Main Methods:

• Genome-wide gene expression profiling of PBMCs from 550 healthy subjects in Italy and Sweden.
• Analysis of annual average NOx exposure data from the ESCAPE study (1990-2006).
• Statistical analyses including univariate analysis, variable selection, gene set enrichment analysis, and assessment of CpG island methylation.

Main Results:

• Long-term NOx exposure was associated with significant changes in gene expression in both Italian and Swedish cohorts.
• Specific genes (AHCYL2, MTMR2) showed alterations in both gene expression and DNA methylation.
• Enrichment analysis revealed overlap between downregulated genes and those known to be affected by cigarette smoking.

Conclusions:

• This study provides evidence that long-term exposure to NOx is associated with subtle but detectable changes in the peripheral blood transcriptome.
• The findings suggest that air pollution may induce molecular changes in the body that share similarities with those caused by tobacco smoke.
• PBMCs represent a valuable resource for studying the molecular impact of environmental exposures.