How to Cite this Article: Monick MM, Beach SR, Plume J, Sears R, Gerrard M, Brody GH, Philibert RA. 2012. Coordinated Changes in AHRR Methylation in Lymphoblasts and Pulmonary Macrophages From Smokers. Am J Med Genet Part B 159B:141–151.
Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers†
Article first published online: 9 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 159B, Issue 2, pages 141–151, March 2012
How to Cite
Monick, M. M., Beach, S. R.H., Plume, J., Sears, R., Gerrard, M., Brody, G. H. and Philibert, R. A. (2012), Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers. Am. J. Med. Genet., 159B: 141–151. doi: 10.1002/ajmg.b.32021
- Issue published online: 12 JAN 2012
- Article first published online: 9 JAN 2012
- Manuscript Accepted: 21 DEC 2011
- Manuscript Received: 14 JUL 2011
- National Institute on Drug Abuse. Grant Number: P30 DA027827, NIH RO1 HL096625, NIH R21HL109589, DA015789, MH080898, and UL1RR024979
Smoking is associated with a wide variety of adverse health outcomes including cancer, chronic obstructive pulmonary disease, diabetes, depression, and heart disease. Unfortunately, the molecular mechanisms through which these effects are conveyed are not clearly understood. To examine the potential role of epigenetic factors in these processes, we examined the relationship of smoking to genome wide methylation and gene expression using biomaterial from two independent samples, lymphoblast DNA and RNA (n = 119) and lung alveolar macrophage DNA (n = 19). We found that in both samples current smoking status was associated with significant changes in DNA methylation, in particular at the aryl hydrocarbon receptor repressor (AHRR), a known tumor suppressor. Both baseline DNA methylation and smoker associated DNA methylation signatures at AHRR were highly correlated (r = 0.94 and 0.45, respectively). DNA methylation at the most differentially methylated AHRR CpG residue in both samples, cg0557592, was significantly associated with AHRR gene expression. Pathway analysis of lymphoblast data (genes with most significant methylation changes) demonstrated enrichment in protein kinase C pathways and in TGF beta signaling pathways. For alveolar macrophages, pathway analysis demonstrated alterations in inflammation-related processes. We conclude that smoking is associated with functionally significant genome wide changes in DNA methylation in both lymphoblasts and pulmonary macrophages and that further integrated investigations of these epigenetic effects of smoking on carcinogenesis and other related co-morbidities are indicated. © 2012 Wiley Periodicals, Inc.