Open Access Research article

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

Meeshanthini V Dogan12, Bridget Shields1, Carolyn Cutrona3, Long Gao2, Frederick X Gibbons4, Ronald Simons5, Martha Monick6, Gene H Brody7, Kai Tan26, Steven RH Beach7 and Robert A Philibert1*

Author Affiliations

1 Department of Psychiatry, University of Iowa, Rm 2-126 MEB, 500 Newton Road, Iowa City, IA 52242, USA

2 Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA

3 Department of Psychology, Iowa State University, Ames, IA, USA

4 Department of Psychology, University of Connecticut, Storrs, CT, USA

5 Department of Sociology, University of Georgia, Athens, GA, USA

6 Department of Internal Medicine, University of Iowa, Iowa City, IA, USA

7 Center for Family Research, University of Georgia, Athens, GA, USA

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BMC Genomics 2014, 15:151  doi:10.1186/1471-2164-15-151

Published: 22 February 2014

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.