Expression of genes involved in stress, toxicity, inflammation, and autoimmunity, and levels of heavy metals in human blood

摘要

Objectives: Exposure to heavy metals is associated with a range of diseases, but the pathways involved are not certain. Abundance of gene (mRNA) transcripts can be measured in participants' blood and contribute to our understanding of how the body reacts to metals. This study aimed to correlate blood levels of three metals (mercury (Hg), cadmium (Cd), and lead (Pb)) with gene expression in 24 participants from the Long Island Study of Seafood Consumption. Methods: We measured Hg, Cd, and Pb in blood, and peripheral blood mRNA expression of 98 genes implicated in stress, toxicity, inflammation, and autoimmunity. We fit multiple linear regression models with multiple testing correction to correlate metals with mRNA abundance. Mean blood Hg was 16.1 μg/L, nearly three times the EPA reference dose (5.8 μg/L); levels of other metals were consistent with background levels (Mean Pb: 2.7 μg/dL; Mean Cd: 0.4 μg/L). Results: Three genes were significantly associated with Hg, four with Cd, and five with Pb, though none were significant after multiple testing correction. We examined whether genes involved in similar/interacting functional pathways, what we refer to as "related genes", showed similar directions of association. IL1RAP, CXCR1, and ITGB2 and their related genes showed negative directions of association with Hg. MMP9 and VEGFA, along with their related genes were positively correlated with Pb. No other related genes showed consistent directions of association. Conclusions: Overall, in this cross-sectional study with one-time measures of metal levels and gene expression, little evidence was found to associate metal exposure with mRNA abundance involved in stress, toxicity, inflammation, and autoimmunity. Potential genes and related genes were suggested for association with specific metals; future work should include larger sample sizes and a wider array of analyzed genes for a more complete picture of physiological reactions to metals exposure.