Demethylation of the aryl hydrocarbon receptor repressor as a biomarker for nascent smokers

Epigenetics. 2012 Nov;7(11):1331-8. doi: 10.4161/epi.22520. Epub 2012 Oct 15.


Epigenetic modifications to peripheral white blood cell DNA occur in response to a wide variety of exposures. In prior work, we and others have shown that broad changes in DNA methylation, particularly at the aryl hydrocarbon receptor repressor (AHRR) locus, occur in samples from subjects with long histories of smoking. However, given the large number of epigenetic changes that occur in response to prolonged smoking, the primacy of the response at AHRR and the sensitivity of these changes to low levels of smoking are not known. Therefore, we examined the association of smoking to genome lymphocyte DNA methylation status in a representative sample of 399 African American youths living in the rural South that includes 72 subjects with less than one half-pack year of exposure. Consistent with our prior findings, we found a stepwise effect of smoking on DNA methylation among youth with relatively brief exposure histories at a CpG residue in AHRR (cg05575921) (FDR corrected p values; 3 × 10 (-7) and 0.09 in the male and female samples, respectively) that was identified in previous studies and at which the effects of smoking were significant, even in those subjects with less than one half pack year exposure. We conclude that AHRR demethylation at cg05575921 in peripheral cells may serve as an early, sensitive biomarker for even low levels of exposure to tobacco smoke, providing a non-self-report alternative for nascent exposure to tobacco smoke. We also suggest that the AHRR/AHR pathway may be functional in the response of peripheral white blood cells to tobacco smoke exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • African Americans
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation*
  • Female
  • Genetic Markers
  • Genome, Human
  • Humans
  • Lymphocytes / metabolism
  • Male
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Smoking / epidemiology
  • Smoking / genetics*
  • Smoking / metabolism
  • Young Adult


  • AHRR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Genetic Markers
  • Repressor Proteins