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The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women.

BMC genomics | Feb 22, 2014

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.

Pubmed ID: 24559495 RIS Download

Mesh terms: Adult | African Americans | Algorithms | Cohort Studies | Computational Biology | CpG Islands | Cytokines | DNA Methylation | Epigenesis, Genetic | Female | Genome-Wide Association Study | Humans | Inflammation Mediators | Leukocytes, Mononuclear | Middle Aged | Protein Interaction Mapping | Protein Interaction Maps | Reproducibility of Results | Sex Factors | Smoking

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Associated grants

  • Agency: NHLBI NIH HHS, Id: R01 HL096625
  • Agency: NHLBI NIH HHS, Id: R21 HL109589
  • Agency: NIEHS NIH HHS, Id: P30 ES005605
  • Agency: NICHD NIH HHS, Id: 5R01HD030588-16A1
  • Agency: NCI NIH HHS, Id: P30 CA086862
  • Agency: NHGRI NIH HHS, Id: R01 HG006130
  • Agency: NIDA NIH HHS, Id: P30 DA027827
  • Agency: NIDA NIH HHS, Id: R21DA034457
  • Agency: NIMH NIH HHS, Id: MH080898

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