Journal article
Coordinated Changes in AHRR Methylation in Lymphoblasts and Pulmonary Macrophages from Smokers
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.159B(2), pp.141-151
03/2012
DOI: 10.1002/ajmg.b.32021
PMCID: PMC3318996
PMID: 22232023
Abstract
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.
Details
- Title: Subtitle
- Coordinated Changes in AHRR Methylation in Lymphoblasts and Pulmonary Macrophages from Smokers
- Creators
- Martha M Monick - Department of Psychiatry, Dartmouth Medical School, Lebanon, NHSteven R.H Beach - Department of Psychiatry, Dartmouth Medical School, Lebanon, NHJeff Plume - Department of Psychiatry, Dartmouth Medical School, Lebanon, NHRory Sears - Department of Psychiatry, Dartmouth Medical School, Lebanon, NHMeg Gerrard - Department of Psychiatry, Dartmouth Medical School, Lebanon, NHGene H Brody - Department of Psychiatry, Dartmouth Medical School, Lebanon, NHRobert A Philibert - Department of Psychiatry, Dartmouth Medical School, Lebanon, NH
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.159B(2), pp.141-151
- DOI
- 10.1002/ajmg.b.32021
- PMID
- 22232023
- PMCID
- PMC3318996
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Grant note
- R21 HL109589-01A1 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 DA015789-05 || DA / National Institute on Drug Abuse : NIDA R01 HL096625-01A1 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL096625-02 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 03/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984003441402771
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