Abstract
BackgroundSmoking 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.ResultsConsistent 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).ConclusionsWe 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.
Highlights
Smoking is the largest preventable cause of morbidity and mortality in the United States
Because our previous work with monoamine oxidase A (MAOA) has shown that smoking cessation is associated with a highly variable remodeling of the MAOA DNA methylation signature, the data from the six subjects with serum cotinine levels
The findings with respect to aryl hydrocarbon receptor repressor (AHRR) extend the prior findings in 19-year-old African American subjects and indicate that smoking induces a steady yet predictable series of changes in the methylation signature of lymphocytes
Summary
Smoking is the largest preventable cause of morbidity and mortality in the United States. 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. 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. Cigarette smoking is a leading preventable cause of mortality in the United States and leads to the premature death of over 100,000 Americans each year [1].
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