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Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation.

ABSTRACT: Smoking is the largest preventable cause of morbidity and mortality in the world. Although there are effective pharmacologic and behavioral treatments for smoking cessation, our inability to objectively quantify smokers' progress in decreasing smoking has been a barrier to both clinical and research efforts. In prior work, we and others have shown that DNA methylation at cg05575921, a CpG residue in the aryl hydrocarbon receptor repressor (AHRR), can be used to determine smoking status and infer cigarette consumption history. In this study, we serially assessed self-report and existing objective markers of cigarette consumption in 35 subjects undergoing smoking cessation therapy, then quantified DNA methylation at cg05575921 at study entry and three subsequent time points. Five subjects who reported serum cotinine and exhaled carbon monoxide verified smoking abstinence for the 3?months prior to study exit averaged a 5.9% increase in DNA methylation at cg05575921 (p?

SUBMITTER: Philibert R

PROVIDER: S-EPMC4822186 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation.

Philibert Robert R Hollenbeck Nancy N Andersen Eleanor E McElroy Shyheme S Wilson Scott S Vercande Kyra K Beach Steven R H SR Osborn Terry T Gerrard Meg M Gibbons Frederick X FX Wang Kai K

Frontiers in psychiatry 20160406

Smoking is the largest preventable cause of morbidity and mortality in the world. Although there are effective pharmacologic and behavioral treatments for smoking cessation, our inability to objectively quantify smokers' progress in decreasing smoking has been a barrier to both clinical and research efforts. In prior work, we and others have shown that DNA methylation at cg05575921, a CpG residue in the aryl hydrocarbon receptor repressor (AHRR), can be used to determine smoking status and infer ...[more]

PMID: 27092088

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Project description:BackgroundNumerous studies have demonstrated that DNA methylation levels in the aryl hydrocarbon receptor repressor (AHRR) gene measured in cord blood are significantly associated with prenatal tobacco smoke exposure and can be used as a fetal exposure biomarker. The mechanism driving this demethylation has not been determined and it is unclear if all cord blood cell types are impacted. Nucleated red blood cells (nRBCs/CD235a+ cells) are developmentally immature RBCs that display genome-wide hypomethylation and are observed at increased frequency in the cord blood of smoking mothers. We tested if AHRR methylation levels in CD235a+ nRBCs or nRBC counts influenced AHRR methylation in whole cord blood.MethodsCord blood was collected from smoking (n = 34) and nonsmoking (n = 19) mothers and DNA was prepared from whole cord blood, isolated CD235a+ nRBCs, and CD14+ monocytes. AHRR methylation in cord blood DNA was measured using Illumina 850K arrays (cg05575921, chr5:373378). Pyrosequencing was used to compare methylation levels among cord blood, CD235a+, and CD14+ cells. We measured nRBC percentages using conventional complete blood counts and estimated percent nRBCs by a deconvolution model.ResultsMethylation levels in AHRR were significantly lower in nRBCs relative to whole cord blood and CD14+ monocytes. While AHRR methylation levels in the cell types were significantly correlated across all subjects, methylation values at the chr5:373378 CpG averaged 14.6% lower in nRBCs (range 0.4 to 24.8%; p = 3.8E-13) relative to CD14+, with nonsmokers showing a significantly greater hypomethylation (- 4.1%, p = 1.8E-02). Methylation level at the AHRR chr5:373378 CpG was strongly associated with self-reported smoking in both CD14+ monocytes (t test p = 5.7E-09) and nRBCs (p = 4.8E-08), as well as cotinine levels (regression p = 1.1E-07 and p = 3.6E-04, respectively). For subjects with whole blood 850K data, robust linear regression models adjusting for estimated cell type composition, either including nRBCs counts or estimates, modestly increased the association between smoking and cg05575921 methylation.ConclusionsPrenatal smoke exposure was highly significantly associated with AHRR methylation in cord blood, CD14+ monocytes, and CD235a+ nRBCs. AHRR methylation levels in nRBCs and nRBC counts had minimal effect on cord blood methylation measurements. However, regression models using estimated nRBCs or actual nRBC counts outperformed those lacking these covariates.

Project description:BackgroundThe number of mobile apps that support smoking cessation is growing, indicating the potential of the mobile phone as a means to support cessation. Knowledge about the potential end users for cessation apps results in suggestions to target potential user groups in a dissemination strategy, leading to a possible increase in the satisfaction and adherence of cessation apps.ObjectiveThis study aimed to characterize potential end users for a specific mobile health (mHealth) smoking cessation app.MethodsA quantitative study was conducted among 955 Dutch smokers and ex-smokers. The respondents were primarily recruited from addiction care facilities and hospitals through Web-based media via websites and forums. The respondents were surveyed on their demographics, smoking behavior, and personal innovativeness. The intention to use and the attitude toward a cessation app were determined on a 5-point Likert scale. To study the association between the characteristics and intention to use and attitude, univariate and multivariate ordinal logistic regression analyses were performed.ResultsThe multivariate ordinal logistic regression showed that the number of previous quit attempts (odds ratio [OR] 4.1, 95% CI 2.4-7.0, and OR 3.5, 95% CI 2.0-5.9) and the score on the Fagerstrom Test of Nicotine Dependence (OR 0.8, 95% CI 0.8-0.9, and OR 0.8, 95% CI 0.8-0.9) positively correlates with the intention to use a cessation app and the attitude toward cessation apps, respectively. Personal innovativeness also positively correlates with the intention to use (OR 0.3, 95% CI 0.2-0.4) and the attitude towards (OR 0.2, 95% CI 0.1-0.4) a cessation app. No associations between demographics and the intention to use or the attitude toward using a cessation app were observed.ConclusionsThis study is among the first to show that demographic characteristics such as age and level of education are not associated with the intention to use and the attitude toward using a cessation app when characteristics related specifically to the app, such as nicotine dependency and the number of quit attempts, are present in a multivariate regression model. This study shows that the use of mHealth apps depends on characteristics related to the content of the app rather than general user characteristics.

Project description:BackgroundGamification in smoking cessation apps has been found to improve cognitive outcomes associated with higher odds of quitting. Although some research has shown that gamification can also positively impact behavioral outcomes such as smoking cessation, studies have largely focused on physical activity and mental health. Only a few studies have explored the effects of gamification on smoking cessation outcomes, of which the majority have adopted qualitative methodologies and/or assessed engagement with apps using self-report.ObjectiveThis study aimed to explore levels of user engagement with gamification features in a smoking cessation app via in-app metrics. Specifically, the objective of this paper was to investigate whether higher engagement with gamification features is associated with the likelihood of quitting in the short term.MethodsData from a larger online study that recruited smokers seeking to quit were analyzed to address the objectives presented in this paper. The study took place between June 2019 and July 2020, and participants were primarily recruited via social media posts. Participants who met the eligibility criteria used 1 of 2 mobile apps for smoking cessation. In-app metrics shared by the developer of one of the smoking cessation apps, called Kwit, were used to assess engagement with gamification features. Out of 58 participants who used the Kwit app, 14 were excluded due to missing data or low engagement with the app (ie, not opening the app once a week). For the remaining 44 participants, mean (SD) values were calculated for engagement with the app using in-app metrics. A logistic regression model was used to investigate the association between engagement with gamification and 7-day smoking abstinence.ResultsIn total, data from 44 participants who used the Kwit app were analyzed. The majority of participants were male, married, and employed. Almost 30% (n=13) of participants self-reported successful 7-day abstinence at the end of the study. On average, the Kwit app was opened almost 31 (SD 39) times during the 4-week study period, with the diary feature used the most often (mean 22.8, SD 49.3). Moreover, it was found that each additional level unlocked was associated with approximately 22% higher odds of achieving 7-day abstinence after controlling for other factors such as age and gender (odds ratio 1.22, 95% CI 1.01-1.47).ConclusionsThis study highlights the likely positive effects of certain gamification elements such as levels and achievements on short-term smoking abstinence. Although more robust research with a larger sample size is needed, this research highlights the important role that gamification features integrated into mobile apps can play in facilitating and supporting health behavior change.

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Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation.

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Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation.

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