title: Allergen sensitization is associated with increased DNA methylation in older men.
abstract: BACKGROUND
  Variation in epigenetic modifications, arising from either environmental exposures or internal physiological changes, can influence gene expression and may ultimately contribute to complex diseases such as asthma and allergies. We examined the association of asthma and allergic phenotypes with DNA methylation levels of retrotransposon-derived elements.
  
  
  METHODS
  We used data from 704 men (mean age 73 years) in the longitudinal Normative Aging Study to assess the relationship between asthma, allergic phenotypes and DNA methylation levels of the retrotransposon-derived elements Alu and long interspersed nuclear element (LINE)-1. Retrotransposons represent a large fraction of the genome (>30%) and are heavily methylated to prevent expression. Percent methylation of Alu and LINE-1 elements in peripheral white blood cells was quantified using PCR pyrosequencing. Data on sensitization to common allergens from skin prick testing, asthma and methacholine responsiveness were gathered approximately 8 years prior to DNA methylation analysis.
  
  
  RESULTS
  Prior allergen sensitization was associated with increased methylation of Alu (β = 0.32 for sensitized vs. nonsensitized patients; p = 0.003) in models adjusted for pack-years of smoking, body mass index, current smoking, air pollutants, percentage of eosinophils, white blood cell count and age. Of the men interviewed, 5% of subjects reported a diagnosis of asthma. Neither Alu nor LINE-1 methylation was associated with asthma.
  
  
  CONCLUSIONS
  These data suggest that increased DNA methylation of repetitive elements may be associated with allergen sensitization but does not appear to be associated with asthma. Future work is needed to identify potential underlying mechanisms for these relationships.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. rejoa@channing.harvard.edu
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Sordillo
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Lange
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Antonella
authors.initials: A
authors.lastname: Zanobetti
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Dawn
authors.initials: D
authors.lastname: Demeo
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
mesh_terms: D000367:Age Factors; D000368:Aged; D000485:Allergens / Q000276:immunology*; D020087:Alu Elements / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D001985:Bronchial Provocation Tests; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D016133:Polymerase Chain Reaction; D012882:Skin Tests
chemical_list: D000485:Allergens; D004247:DNA