title: Psychological factors and DNA methylation of genes related to immune/inflammatory system markers: the VA Normative Aging Study.
abstract: OBJECTIVE
  Although psychological factors have been associated with chronic diseases such as coronary heart disease (CHD), the underlying pathways for these associations have yet to be elucidated. DNA methylation has been posited as a mechanism linking psychological factors to CHD risk. In a cohort of community-dwelling elderly men, we explored the associations between positive and negative psychological factors with DNA methylation in promoter regions of multiple genes involved in immune/inflammatory processes related to atherosclerosis.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Greater Boston, Massachusetts area.
  
  
  METHODS
  Samples of 538 to 669 men participating in the Normative Aging Study cohort with psychological measures and DNA methylation measures, collected on 1-4 visits between 1999 and 2006 (mean age=72.7 years at first visit).
  
  
  METHODS
  We examined anxiety, depression, hostility and life satisfaction as predictors of leucocyte gene-specific DNA methylation. We estimated repeated measures linear mixed models, controlling for age, smoking, education, history of heart disease, stroke or diabetes, % lymphocytes, % monocytes and plasma folate.
  
  
  RESULTS
  Psychological distress measured by anxiety, depression and hostility was positively associated, and happiness and life satisfaction were inversely associated with average Intercellular Adhesion Molecule-1 (ICAM-1) and coagulation factor III (F3) promoter methylation levels. There was some evidence that hostility was positively associated with toll-like receptor 2 (TLR-2) promoter methylation, and that life satisfaction was inversely associated with TLR-2 and inducible nitric oxide synthase (iNOS) promoter methylation. We observed less consistent and significant associations between psychological factors and average methylation for promoters of the genes for glucocorticoid receptor (NR3C1), interferon-γ (IFN-γ) and interleukin 6 (IL-6).
  
  
  CONCLUSIONS
  These findings suggest that positive and negative psychological factors affect DNA methylation of selected genes involved in chronic immune/inflammatory processes and inflammation-related endothelial dysfunction. Such epigenetic changes may represent biological pathways that mediate the effects of psychological factors on CHD.
authors.affiliation: Department of Health Sciences, Northeastern University, Boston, Massachusetts, USA Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts, USA Department of Human and Social Sciences, EHESP French School of Public Health, Rennes, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kubzansky
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts, USA VA Normative Aging Study, VA Boston Healthcare System, Boston, Massachusetts, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.affiliation: VA Normative Aging Study, VA Boston Healthcare System, Boston, Massachusetts, USA Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Avron
authors.initials: A
authors.lastname: Spiro
authors.affiliation: University of Milan, Milan, Italy IRCCS Maggiore Policlinico Hospital, Milan, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.affiliation: University of Milan, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cantone
authors.affiliation: VA Normative Aging Study, VA Boston Healthcare System, Boston, Massachusetts, USA Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000523:psychology; D001007:Anxiety / Q000150:complications / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000523:psychology*; D015415:Biomarkers; D001900:Boston; D019175:DNA Methylation; D003863:Depression / Q000150:complications / Q000235:genetics*; D044127:Epigenesis, Genetic; D005819:Genetic Markers; D006791:Hostility; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000523:psychology; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010549:Personal Satisfaction; D011446:Prospective Studies; D058014:Veterans Health
chemical_list: D015415:Biomarkers; D005819:Genetic Markers
keywords: methylation; psycholoogical factors