title: DNA methylation in inflammatory genes among children with obstructive sleep apnea.
abstract: BACKGROUND
  Pediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions.
  
  
  METHODS
  DNA from matched children with OSA with and without high levels of high-sensitivity C-reactive protein (hsCRP) were assessed for DNA methylation levels of 24 inflammatory-related genes. Primer-based polymerase chain reaction assays in a case-control setting involving 47 OSA cases and 31 control subjects were conducted to confirm the findings; hsCRP and myeloid-related protein (MRP) 8/14 levels were also assayed.
  
  
  RESULTS
  Forkhead box P3 (FOXP3) and interferon regulatory factor 1 (IRF1) showed higher methylation in six children with OSA and high hsCRP levels compared with matched children with OSA and low hsCRP levels (P < 0.05). In the case-control cohort, children with OSA and high CRP levels had higher log FOXP3 DNA methylation levels compared with children with OSA and low CRP levels and control subjects. IRF1 did not exhibit significant differences. FOXP3 DNA methylation levels correlated with hsCRP and MRP 8/14 levels and with apnea-hypopnea index (AHI), BMI z score, and apolipoprotein B levels. A stepwise multiple regression model showed that AHI was independently associated with FOXP3 DNA methylation levels (P < 0.03).
  
  
  CONCLUSIONS
  The FOXP3 gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with OSA who exhibit increased systemic inflammatory responses. Thus, epigenetic modifications may constitute an important determinant of inflammatory phenotype in OSA, and FOXP3 DNA methylation levels may provide a potential biomarker for end-organ vulnerability.
authors.affiliation: Section of Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Illinois 60637, USA.
authors.forename: Jinkwan
authors.initials: J
authors.lastname: Kim
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhattacharjee
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.forename: Leila
authors.initials: L
authors.lastname: Kheirandish-Gozal
authors.forename: Oscar Sans
authors.initials: OS
authors.lastname: Capdevila
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism; D040501:Calgranulin A / Q000097:blood; D040502:Calgranulin B / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D017286:Polysomnography; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000235:genetics*
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D008055:Lipids; D002097:C-Reactive Protein
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