Changes in DNA methylation at the aryl hydrocarbon receptor repressor may be a new biomarker for smoking

Smoking is the largest preventable cause of morbidity and mortality in the United States. In previous work, we demonstrated that altered DNA methylation at the aryl hydrocarbon receptor repressor (AHRR) is correlated with self-reported smoking in 19-year-old African Americans with relatively low levels of smoking. However, one limitation of the prior work is that it was based on self-reported data only. Therefore, the relationship of AHRR methylation to smoking in older subjects and to indicators such as serum cotinine levels remains unknown. To address this question, we examined the relationship between genome- wide DNA methylation and smoking status as indicated by serum cotinine levels in a cohort of 22-year-old African American men.

Consistent with prior findings, smoking was associated with significant DNA demethylation at two distinct loci within AHRR (cg05575921 and cg21161138) with the degree of demethylation being greater than that observed in the prior cohort of 19-year-old smoking subjects. Additionally, methylation status at the AHRR residue interrogated by cg05575921 was highly correlated with serum cotinine levels (adjusted R2 = 0.42, P < 0.0001).

We conclude that AHRR DNA methylation status is a sensitive marker of smoking history and could serve as a biomarker of smoking that could supplement self-report or existing biomarker measures in clinical or epidemiological analyses of the effects of smoking. In addition, if properly configured as a clinical assay, the determination of AHRR methylation could also be used as a screening tool in efforts to target antismoking interventions to nascent smokers in the early phases of smoking.