Particulate matter exposure is associated with inflammatory gene methylation in obese subjects

Background: Overweight and obesity are becoming more widespread with alarming projections for the coming years. Obesity may increase susceptibility to the adverse effects of PM exposure, exacerbating the effects on cardiovascular diseases and altering the biomarkers of vascular inflammation. The associated biological mechanisms have not been fully understood yet; the common denominator in the pathogenesis of the co morbidities of obesity is the presence of an active, low-grade inflammatory process. DNA methylation has been shown to regulate inflammatory pathways that are responsible for the development of cardiovascular diseases. Objectives: The aim of the study was to investigate, in a population of overweight/obese subjects, the effects of PM on blood DNA methylation in genes associated to inflammatory response. Methods: Using bisulfite pyrosequencing, we measured DNA methylation in peripheral blood mononuclear cells from 186 overweighted/obese subjects. In particular, we quantified DNA methylation in a set of 3 candidate genes, including CD14, TLR4 and TNF-alpha, because of the important roles that these genes play in the inflammatory pathway. Personal exposure to PM10 was estimated for each subject based on the local PM10 concentrations, measured by monitoring stations at residential address. Repeated measure models were used to evaluate the association of PM10 with each genes, accounting for possible correlations among the genes that regulate the same inflammatory pathway. Results: We found an inverse association between the daily PM10 exposure and the DNA methylation of inflammatory genes, measured in peripheral blood of healthy overweight/obese subjects. Considering different exposure time-windows, the effect on CD14 and TLR4 methylation was observed, respectively, in days 4-5-6, and days 6-7-8. TNF-alpha methylation was not associated to PM10. Conclusions: Our findings support a picture in which PM10 exposure and transcriptional regulation of inflammatory gene pathway in obese subjects are associated.