The Reversion of cg05575921 Methylation in Smoking Cessation: A Potential Tool for Incentivizing Healthy Aging

Abstract

Smoking is the largest preventable cause of mortality and the largest environmental driver of epigenetic aging. Contingency management-based strategies can be used to treat smoking but require objective methods of verifying quitting status. Prior studies have suggested that cg05575921 methylation reverts as a function of smoking cessation, but that it can be used to verify the success of smoking cessation has not been unequivocally demonstrated. To test whether methylation can be used to verify cessation, we determined monthly cg05575921 levels in a group of 67 self-reported smokers undergoing biochemically monitored contingency management-based smoking cessation therapy, as part of a lung imaging protocol. A total of 20 subjects in this protocol completed three months of cotinine verified smoking cessation. In these 20 quitters, the reversion of cg05575921 methylation was dependent on their initial smoking intensity, with methylation levels in the heaviest smokers reverting to an average of 0.12% per day over the 3-month treatment period. In addition, we found suggestive evidence that some individuals may have embellished their smoking history to gain entry to the study. Given the prominent effect of smoking on longevity, we conclude that DNA methylation may be a useful tool for guiding and incentivizing contingency management-based approaches for smoking cessation.

The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies

“…The Smoking Computerized Tomography (SCT) cohort was collected as part of a project whose purpose was to understand the relationship of sildenafil on pulmonary 28 . In this protocol, subjects who smoked at least 10 cigarettes per day and had a 5-pack year history of smoking were invited to complete a REDCap® administered prescreening interview to assess smoking history and study eligibility.…”

The Reversion of DNA Methylation at Coronary Heart Disease Risk Loci in Response to Prevention Therapy

“…Fortunately, the use of cg05575921 as a metric for change in smoking intensity permits the stable objective measurement of smoking intensity [17,19]. Recently, we have shown that changes in cg05575921 methylation in response to smoking cessation are also dosedependent [16]. Therefore, in order to determine whether the changes in smoking intensity were related to the changes in methylation, we analyzed the relationship of the change of methylation at each of the cardiac markers to the change in smoking intensity as measured by change in cg05575921.…”

“…However, CHD prevention has no such social stigma, and recent work with biomarkers of hepatic injury has shown the benefit of physicians conveying similar information about the protective effects of alcohol cessation on liver function to patients with alcohol dependence [27]. Using potential effects of smoking cessation on CHD risk, alone or together with incentive-based programming methods for smoking cessation, could be a powerful motivator to persuade nicotine-dependent smokers to quit [16].…”

“…Study Participants: The 39 participants whose data are included in this study were part of a cohort of 67 subjects recruited in a series of advertisements seeking adult daily smokers, distributed to patients and staff at the University of Iowa Hospitals and Clinics [16]. Those subjects who were potentially interested in the study were invited to complete an online survey on their smoking habits.…”

“…However, we recently completed a study of the effects of smoking cessation on pulmonary inflammation. In that study, subjects were offered USD 400 of financial incentive to quit smoking without the use of smoking cessation agents-in particular, nicotine replacement therapy [16]. In total, 20 subjects completed 3 months of cotinine-verified smoking cessation and provided DNA samples before and after 3 months of biochemically verified smoking cessation.…”