title: DNA methylation of the allergy regulatory gene interferon gamma varies by age, sex, and tissue type in asthmatics.
abstract: BACKGROUND
  Asthma is associated with allergic sensitization in about half of all cases, and asthma phenotypes can vary by age and sex. DNA methylation in the promoter of the allergy regulatory gene interferon gamma (IFNγ) has been linked to the maintenance of allergic immune function in human cell and mouse models. We hypothesized that IFNγ promoter methylation at two well-studied, key cytosine phosphate guanine (CpG) sites (-186 and -54), may differ by age, sex, and airway versus systemic tissue in a cohort of 74 allergic asthmatics.
  
  
  RESULTS
  After sampling buccal cells, a surrogate for airway epithelial cells, and CD4+ lymphocytes, we found that CD4+ lymphocyte methylation was significantly higher in children compared to adults at both CpG sites (P <0.01). Buccal cell methylation was significantly higher in children at CpG -186 (P = 0.03) but not CpG -54 (P = 0.66). Methylation was higher in males compared to females at both CpG sites in CD4+ lymphocytes (-186: P <0.01, -54: P = 0.02) but not buccal cells (-186: P = 0.14, -54: P = 0.60). In addition, methylation was lower in CD4+ lymphocytes compared to buccal cells (P <0.01) and neighboring CpG sites were strongly correlated in CD4+ lymphocytes (r = 0.84, P <0.01) and weakly correlated in buccal cells (r = 0.24, P = 0.04). At CpG -186, there was significant correlation between CD4+ lymphocytes and buccal cells (r = 0.24, P = 0.04) but not at CpG -54 (r = -0.03, P = 0.78).
  
  
  CONCLUSIONS
  These findings highlight significant age, sex, and tissue-related differences in IFNγ promoter methylation that further our understanding of methylation in the allergic asthma pathway and in the application of biomarkers in clinical research.
authors.affiliation: Division of Pediatric Pulmonology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, 3959 Broadway CHC-737, New York, NY 10032, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lovinsky-Desir
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, NY 10032, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ridder
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, NY 10032, USA.
authors.forename: David
authors.initials: D
authors.lastname: Torrone
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, NY 10032, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Maher
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, NY 10032, USA.
authors.forename: Surinder
authors.initials: S
authors.lastname: Narula
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, NY 10032, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Scheuerman
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168 St, New York, NY 10032, USA.
authors.forename: David
authors.initials: D
authors.lastname: Merle
authors.affiliation: Division of Pediatric Pulmonology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, 3959 Broadway CHC-737, New York, NY 10032, USA.
authors.forename: Meyer
authors.initials: M
authors.lastname: Kattan
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, NY 10032, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: DiMango
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, NY 10032, USA ; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W 168 St, New York, NY 10032, USA ; Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W 168 St, New York, New York 10032, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Miller
keywords: Age-related methylation; Asthma; Buccal cells; CD4+ lymphocytes; Epigenetics; Interferon gamma; Methylation; Sex-related methylation; Tissue specific methylation