title: Life-course socioeconomic status and DNA methylation of genes regulating inflammation.
abstract: BACKGROUND
  In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment.
  
  
  METHODS
  The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study.
  
  
  RESULTS
  Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease risk.
authors.affiliation: Institute of Social and Preventive Medicine, University Hospital Centre, Lausanne, Switzerland, silvia.stringhini@chuv.ch.
authors.forename: Silvia
authors.initials: S
authors.lastname: Stringhini
authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Polidoro
authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Kelly
authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy, MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
authors.forename: Karin
authors.initials: K
authors.lastname: van Veldhoven
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Grioni
authors.affiliation: Cancer Registry, ASP Ragusa, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Cancer Registry, ASP Ragusa, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Giurdanella
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Centre of Primary Care and Public Health Blizard Institute Queen Mary, University of London, UK and Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gallo
authors.affiliation: MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
authors.forename: Raphaële
authors.initials: R
authors.lastname: Castagné
authors.affiliation: Institute of Social and Preventive Medicine, University Hospital Centre, Lausanne, Switzerland.
authors.forename: Fred
authors.initials: F
authors.lastname: Paccaud
authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Campanella
authors.affiliation: MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Chadeau-Hyam
authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy, MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
mesh_terms: D019175:DNA Methylation; D005260:Female; D055106:Genome-Wide Association Study; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D050778:NFATC Transcription Factors / Q000235:genetics*; D011446:Prospective Studies; D012923:Social Class; D012931:Social Environment
chemical_list: D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human
keywords: DNA methylation; inflammation; life course; socioeconomic status