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

Abstract

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.

Keywords: :

• aryl hydrocarbon receptor repressor
• smoking
• biomarker
• lymphocytes
• DNA methylation
• epigenetics

Disclosure of Potential Conflicts of Interest

The University of Iowa has filed intellectual property right claims on some of the material related to this manuscript on behalf of Dr Philibert. Drs Beach and Brody do not have any conflicts to disclose.

Acknowledgments

The work in this study was supported by 5R01HD030588-16A1 to G.H.B. and R21DA034457 to R.A.P. Additional support for these studies was derived from the Center for Contextual Genetics and Prevention Science (Grant Number P30 DA027827, GB) funded by the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The University of Iowa has filed intellectual property right claims on some of the material related to this manuscript on behalf of

Supplemental Materials

Supplemental materials may be found here: www.landesbioscience.com/journals/epigenetics/article/22520