Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution.

Katerina Honkova,Hasmik Margaryan,Pavel Rossner,Alena Milcova,Jiri Rubes,Irena Chvojkova,Vitezslav Jirik,Jan Topinka,Radim J Sram,Andrea Rossnerova,Anna Pastorkova,Antonin Ambroz

doi:10.3390/ijms23031666

Abstract

DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city policemen (sampled twice), living and working in three localities (Prague, Ostrava and Ceske Budejovice) of the Czech Republic, who spent the majority of their working time outdoors. The main characterization of the localities, differing by major sources of air pollution, was defined by the stationary air pollution monitoring of PM2.5, B[a]P and NO2. DNA methylation was analyzed by a genome-wide microarray method. No season-specific DNA methylation pattern was discovered; however, we identified 13,643 differentially methylated CpG loci (DML) for a comparison between the Prague and Ostrava groups. The most significant DML was cg10123377 (log2FC = −1.92, p = 8.30 × 10−4) and loci annotated to RPTOR (total 20 CpG loci). We also found two hypomethylated loci annotated to the DNA repair gene XRCC5. Groups of DML annotated to the same gene were linked to diabetes mellitus (KCNQ1), respiratory diseases (PTPRN2), the dopaminergic system of the brain and neurodegenerative diseases (NR4A2). The most significant possibly affected pathway was Axon guidance, with 86 potentially deregulated genes near DML. The cluster of gene sets that could be affected by DNA methylation in the Ostrava groups mainly includes the neuronal functions and biological processes of cell junctions and adhesion assembly. The study demonstrates that the differences in the type of air pollution between localities can affect a unique change in DNA methylation profiles across the human genome.

Highlights

Long-term exposure to air pollutants has an adverse health impact and affects the genome and epigenome [1]
DNA methylation can serve as a useful biomarker of exposure, and an analysis of DNA methylation gives a better understanding of the effects of environmental exposure, as well as the role of epigenetic mechanisms, on human health [3,4]
We aimed to find specific DNA methylation patterns based on the quantitative data of the annotated 856,865 CpG sites, which could be characterized by work and life in environments affected by different types of air pollution

Summary

Introduction

Long-term exposure to air pollutants has an adverse health impact and affects the genome and epigenome [1]. DNA methylation is one of the most studied epigenetic mechanisms that regulates gene expression and affects genome stability [2]. DNA methylation can serve as a useful biomarker of exposure, and an analysis of DNA methylation gives a better understanding of the effects of environmental exposure, as well as the role of epigenetic mechanisms, on human health [3,4]. A commonly used method is quantitative global DNA methylation, which represents an effective, fast and cheap solution [11,12]. This method cannot distinguish between important hypo- and hypermethylated sites. Other methods are used in epigenome-wide association studies (EWAS) [13]; these are currently mostly based on gene-specific genome-wide DNA methylation (microarray approaches)

Objectives

Methods

Results

Discussion

Conclusion