title: The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women.
abstract: BACKGROUND
  Regular smoking is associated with a wide variety of syndromes with prominent inflammatory components such as cancer, obesity and type 2 diabetes. Heavy regular smoking is also associated with changes in the DNA methylation of peripheral mononuclear cells. However, in younger smokers, inflammatory epigenetic findings are largely absent which suggests the inflammatory response(s) to smoking may be dose dependent. To help understand whether peripheral mononuclear cells have a role in mediating these responses in older smokers with higher cumulative smoke exposure, we examined genome-wide DNA methylation in a group of well characterized adult African American subjects informative for smoking, as well as serum C-reactive protein (CRP) and interleukin-6 receptor (IL6R) levels. In addition, complementary bioinformatic analyses were conducted to delineate possible pathways affected by long-term smoking.
  
  
  RESULTS
  Genome-wide DNA methylation analysis with respect to smoking status yielded 910 significant loci after Benjamini-Hochberg correction. In particular, two loci from the AHRR gene (cg05575921 and cg23576855) and one locus from the GPR15 gene (cg19859270) were identified as highly significantly differentially methylated between smokers and non-smokers. The bioinformatic analyses showed that long-term chronic smoking is associated with altered promoter DNA methylation of genes coding for proteins mapping to critical sub-networks moderating inflammation, immune function, and coagulation.
  
  
  CONCLUSIONS
  We conclude that chronic regular smoking is associated with changes in peripheral mononuclear cell methylation signature which perturb inflammatory and immune function pathways and may contribute to increased vulnerability for complex illnesses with inflammatory components.
authors.forename: Meeshanthini V
authors.initials: MV
authors.lastname: Dogan
authors.forename: Bridget
authors.initials: B
authors.lastname: Shields
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cutrona
authors.forename: Long
authors.initials: L
authors.lastname: Gao
authors.forename: Frederick X
authors.initials: FX
authors.lastname: Gibbons
authors.forename: Ronald
authors.initials: R
authors.lastname: Simons
authors.forename: Martha
authors.initials: M
authors.lastname: Monick
authors.forename: Gene H
authors.initials: GH
authors.lastname: Brody
authors.forename: Kai
authors.initials: K
authors.lastname: Tan
authors.forename: Steven R H
authors.initials: SR
authors.lastname: Beach
authors.affiliation: Department of Psychiatry, University of Iowa, Rm 2-126 MEB, 500 Newton Road, Iowa City, IA 52242, USA. robert-philibert@uiowa.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Philibert
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000465:Algorithms; D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D016207:Cytokines / Q000097:blood; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D015203:Reproducibility of Results; D012737:Sex Factors; D012907:Smoking
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators