title: DNA methylation and childhood asthma in the inner city.
abstract: BACKGROUND
  Epigenetic marks are heritable, influenced by the environment, direct the maturation of T lymphocytes, and in mice enhance the development of allergic airway disease. Thus it is important to define epigenetic alterations in asthmatic populations.
  
  
  OBJECTIVE
  We hypothesize that epigenetic alterations in circulating PBMCs are associated with allergic asthma.
  
  
  METHODS
  We compared DNA methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy control subjects by using DNA and RNA from PBMCs. Results were validated in an independent population of asthmatic patients.
  
  
  RESULTS
  Comparing asthmatic patients (n = 97) with control subjects (n = 97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthma, including IL13, RUNX3, and specific genes relevant to T lymphocytes (TIGIT). Among asthmatic patients, 11 differentially methylated regions were associated with higher serum IgE concentrations, and 16 were associated with percent predicted FEV1. Hypomethylated and hypermethylated regions were associated with increased and decreased gene expression, respectively (P < 6 × 10(-12) for asthma and P < .01 for IgE). We further explored the relationship between DNA methylation and gene expression using an integrative analysis and identified additional candidates relevant to asthma (IL4 and ST2). Methylation marks involved in T-cell maturation (RUNX3), TH2 immunity (IL4), and oxidative stress (catalase) were validated in an independent asthmatic cohort of children living in the inner city.
  
  
  CONCLUSIONS
  Our results demonstrate that DNA methylation marks in specific gene loci are associated with asthma and suggest that epigenetic changes might play a role in establishing the immune phenotype associated with asthma.
authors.affiliation: Department of Medicine, University of Colorado, School of Medicine, Aurora, Colo; Departments of Pediatrics and Medicine, National Jewish Health, Denver, Colo.
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.affiliation: Department of Medicine, University of Colorado, School of Medicine, Aurora, Colo.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Pedersen
authors.affiliation: Departments of Pediatrics and Medicine, National Jewish Health, Denver, Colo.
authors.forename: Andrew
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Mass.
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.affiliation: Children's National Health System, Washington, DC.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Teach
authors.affiliation: Columbia University Medical Center, New York, NY.
authors.forename: Meyer
authors.initials: M
authors.lastname: Kattan
authors.affiliation: Department of Medicine, Henry Ford Hospital, Detroit, Mich.
authors.forename: Rana Tawil
authors.initials: RT
authors.lastname: Misiak
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, Tex.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gruchalla
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Mass.
authors.forename: Suzanne F
authors.initials: SF
authors.lastname: Steinbach
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado and University of Colorado, School of Medicine, Aurora, Colo.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.affiliation: University of Texas, Southwestern Medical Center, Dallas, Tex.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Gill
authors.affiliation: Rho Federal Systems Division, Chapel Hill, NC.
authors.forename: Agustin
authors.initials: A
authors.lastname: Calatroni
authors.affiliation: Rho Federal Systems Division, Chapel Hill, NC.
authors.forename: Gloria
authors.initials: G
authors.lastname: David
authors.affiliation: Department of Medicine, University of Colorado, School of Medicine, Aurora, Colo.
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Hennessy
authors.affiliation: Department of Medicine, University of Colorado, School of Medicine, Aurora, Colo.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Davidson
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, Colo.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Peter
authors.initials: P
authors.lastname: Gergen
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Alkis
authors.initials: A
authors.lastname: Togias
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Department of Medicine, University of Colorado, School of Medicine, Aurora, Colo; Departments of Pediatrics and Medicine, National Jewish Health, Denver, Colo; Department of Immunology, University of Colorado, Aurora, Colo. Electronic address: david.schwartz@ucdenver.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002648:Child; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D004247:DNA / Q000032:analysis*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D012313:RNA / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D012129:Respiratory Function Tests; D014505:Urban Population
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C493729:Runx3 protein, human; C534712:TIGIT protein, human; D015847:Interleukin-4; D007073:Immunoglobulin E; D012313:RNA; D004247:DNA
keywords: DNA methylation; T(H)2 immunity; atopic asthma; epigenetics; inner city