title: Particulate matter exposure is associated with inflammatory gene methylation in obese subjects.
abstract: 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.
  
  
  OBJECTIVE
  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-α, because of the important roles that these genes play in the inflammatory pathway. Personal exposure to PM10was estimated for each subject based on the local PM10concentrations, 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 PM10exposure 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-α methylation was not associated to PM10.
  
  
  CONCLUSIONS
  Our findings support a picture in which PM10exposure and transcriptional regulation of inflammatory gene pathway in obese subjects are associated.
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab., Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. Electronic address: laura.cantone@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Cantone
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab., Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Iodice
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab., Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab., Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Albetti
authors.affiliation: Department of Preventive Medicine, UOC Protezione e Promozione Salute Lavoratori Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Restelli
authors.affiliation: Department of Preventive Medicine, UOC Protezione e Promozione Salute Lavoratori Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Luisella
authors.initials: L
authors.lastname: Vigna
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab., Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Department of Preventive Medicine, UOC Protezione e Promozione Salute Lavoratori Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonzini
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab., Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Angela Cecilia
authors.initials: AC
authors.lastname: Pesatori
authors.affiliation: EPIGET - Epidemiology, Epigenetics and Toxicology Lab., Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
mesh_terms: D000328:Adult; D000368:Aged; D001774:Blood Chemical Analysis; D019175:DNA Methylation; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000453:epidemiology*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000139:chemically induced / Q000453:epidemiology*; D050177:Overweight / Q000139:chemically induced / Q000453:epidemiology*; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D052638:Particulate Matter
keywords: DNA methylation; Inflammation; Obesity; PM exposure; Pyrosequencing