DNA methylation: a potential mediator between air pollution and metabolic syndrome

Given the global increase in air pollution and its crucial role in human health, as well as the steep rise in prevalence of metabolic syndrome (MetS), a better understanding of the underlying mechanisms by which environmental pollution may influence MetS is imperative. Exposure to air pollution is known to impact DNA methylation, which in turn may affect human health. This paper comprehensively reviews the evidence for the hypothesis that the effect of air pollution on the MetS is mediated by DNA methylation in blood. First, we present a summary of the impact of air pollution on metabolic dysregulation, including the components of MetS, i.e., disorders in blood glucose, lipid profile, blood pressure, and obesity. Then, we provide evidence on the relation between air pollution and endothelial dysfunction as one possible mechanism underlying the relation between air pollution and MetS. Subsequently, we review the evidence that air pollution (PM, ozone, NO2 and PAHs) influences DNA methylation. Finally, we summarize association studies between DNA methylation and MetS. Integration of current evidence supports our hypothesis that methylation may partly mediate the effect of air pollution on MetS. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-022-01301-y.


Supplementary
China Cross-sectional/65 Adults -Exposure to ambient air pollutants (PM2.5) is associated with higher blood pressure and insuline resistance.
Poursafa et al [29] Iran (IR) Nationwide study/1,413 children -Living in areas with higher air pollution leads to higher levels of MetS components including increased systolic blood pressure, fasting blood glucose, and triglycerides, as well as lower levels of HDL-C. Acute exposure to ambient ozone was associated with higher blood pressure and with increased serum levels of angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) as biomarkers of blood pressure. Bead Chip/Blood 31 CpGs showed significant association with blood pressure, 13 of which were independently replicated. Six of the identified CpG sites also showed significant association with gene expression (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3).

Study design/Study population Methods/Tissue Main Findings
Huang et al [111] European and African

EWAS/4,820 individuals
Meta-analysis 34 CpGs showed significant association with blood pressure. Six of the identified CpG sites also showed significant association (FDR < 0.05) with gene expression (PHGDH,ABCG1,LMNA,RBPMS2,and SLC1A5). Further investigation of these CpG sites in a meta-analysis of twin cohorts suggested that the majority of correlation between DNA methylation and blood pressure can be explained by shared environmental factors. BeadChip/Blood 76 obesity-related CpG sites were identified, 54 of which were validated. Sixteen CpG sites were associated with expression of 17 genes in cis, of which 5 genes displayed differential expression between obese cases and lean controls.

Air pollutant Measurement Method Description
Ozone (O3) -UV Photometric -Chemiluminescence Represents a variation of the ultraviolet (UV) photometric method, known as the "scrubberless" UV (SL-UV) method that specifies removal of O3 from the sampled air.
Utilizes Nitric Oxide to measure ozone in the atmosphere where the reaction between ambient ozone and NO produce light proportional to the ozone concentration.
Particulate Matter (PM) Beta attenuation monitoring (BAM) Absorption of beta radiation by solid particles extracted from air flow.

Carbon Monoxide (CO) Nondispersive infrared (NDIR) technique
The NDIR technique is an automated and continuous method that is based on the specific absorption of infrared radiation by the CO molecule.
Sulfur Dioxide (SO2) Ultraviolet fluorescence SO2 molecules absorb UV light and become excited at one wavelength, then decay to a lower energy state emitting UV light at a different wavelength.
Nitrogen Dioxide (NO2) Chemiluminescence Measurement of light produced by the gasphase titration of nitric oxide and ozone.
NO + O3 → NO2 + O2 + light emission. Minimum P value of methylation sites on each gene is given (minP), alongside with its corresponding effect direction. All results are from whole/cord blood samples. AP: Air Pollution; PM: Particulate Matter.