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Refinement of cg05575921 demethylation response in nascent smoking.

ABSTRACT: The initiation of adolescent smoking is difficult to detect using carbon monoxide or cotinine assays. Previously, we and others have shown that the methylation of cg05575921 is an accurate predictor of adult smoking status. But the dose and time dependency of the demethylation response to smoking initiation in adolescents is not yet well understood. To this end, we conducted three consecutive annual in-person interviews and biological samplings of 448 high school students (wave 1 (W1)-wave 3 (W3)). At W1 (n = 448), 62 subjects reported using tobacco and 72 subjects reported using cannabis at least once in their life-time with 38 and 20 subjects having a positive cotinine and cannabinoid levels, respectively, at W1 intake. At W3 (n = 383), 67 subjects reported using tobacco and 60 subjects reported using cannabis at least once with 75 and 60 subjects having positive cotinine and cannabinoid levels, respectively, at W3. Subjects with undetectable cotinine levels at all three-time waves had stable levels of cg05575921 methylation throughout the study (88.7% at W1 and 88.8% at W3, n = 149), while subjects with positive cotinine levels at all 3 time points manifested a steady decrease in cg05575921 methylation (81.8% at W1 and 71.3% at the W3, n = 12). In those subjects with an affirmative smoking self-report at W3 (n = 17), the amount of demethylation at cg05575921 was correlated with time and intensity of smoking. We conclude that cg05575921 methylation is a sensitive, dose-dependent indicator of early stages of smoking, and may help to identify smokers in the early stages of smoking.

SUBMITTER: Dawes K

PROVIDER: S-EPMC7315557 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Refinement of cg05575921 demethylation response in nascent smoking.

Dawes Kelsey K Andersen Allan A Papworth Emma E Hundley Brandon B Hutchens Natasha N El Manawy Heba H Becker Ashley A Sampson Luke L Philibert Willem W Gibbons Frederick X FX Gerrard Meg M Philibert Robert R

Clinical epigenetics 20200624 1

The initiation of adolescent smoking is difficult to detect using carbon monoxide or cotinine assays. Previously, we and others have shown that the methylation of cg05575921 is an accurate predictor of adult smoking status. But the dose and time dependency of the demethylation response to smoking initiation in adolescents is not yet well understood. To this end, we conducted three consecutive annual in-person interviews and biological samplings of 448 high school students (wave 1 (W1)-wave 3 (W3 ...[more]

PMID: 32580755

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Project description:Objectives: Early identification of smoking, essential for the successful implementation of interventions, arrests the escalation of smoking and smoking-associated risk behaviors in adolescents. However, because nascent smoking is typically episodic and infrequent, enzyme-linked immunoassay reagent-based approaches that detect cotinine, a key nicotine metabolite, are not effective in identifying adolescents in the earliest stages of smoking. Epigenetic methods may offer an alternative approach for detecting early-stage smokers. In prior work, we and others have shown that the methylation status of cg05575921 of whole-blood DNA accurately predicts smoking status in regularly smoking adults and is sensitive to nascent smoking. Yet, the blood draws necessary to obtain DNA for this method may be poorly accepted by adolescents. Saliva could be an alternative source of DNA. However, the ability of saliva DNA methylation status to predict smoking status among adolescents is unknown. Methods: To explore the possibility of using salivary DNA for screening purposes, we examined the DNA methylation status at cg05575921 in saliva DNA samples from 162 high school aged subjects for whom we also had paired serum cotinine values. Results: Overall, the reliability of self-report of nicotine/tobacco use in these adolescents was poor with 67% of all subjects whose serum levels of cotinine was ?2?ng/mL (n?=?75) denying any use of nicotine-containing products in the past 6 months. However, the correspondence of the two biological measures of smoking was high, with serum cotinine positivity being strongly correlated with cg05575921 methylation (p?<?0.0001). Receiver operating characteristic (ROC) analyses showed that cg05575921 methylation status could be used to classify those with positive serum cotinine values (?2?ng/mL) from those denying smoking and have undetectable levels of cotinine. Conclusions: We conclude that saliva DNA methylation assessments hold promise as a means of detecting nascent smoking.

Project description:BackgroundDNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels.MethodsData on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008-2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30-70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions.ResultsLiving in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (β = - 0.01003, P = 0.009 and β = - 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels.ConclusionLiving in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease.

Project description:BackgroundPolycyclic aromatic hydrocarbon (PAH)-rich substances like cigarette smoke and PM2.5 induce aryl hydrocarbon receptor (AHR)-mediated aryl hydrocarbon receptor repressor (AHRR) methylation. AHRR cg05575921 and coagulation factor II (thrombin) receptor-like 3 (F2RL3) cg03636183 methylation patterns are well-established biomarkers for smoking. Even though AHRR cg05575921 methylation has recently been associated with PM2.5, the interaction between smoking and PM2.5 on AHRR methylation is yet to be fully explored. We evaluated AHRR and F2RL3 CpG sites to identify potential significant markers in relation to PM2.5 and smoking in Taiwanese adults.MethodsDNA methylation and smoking data of 948 participants aged 30-70 years were obtained from the Taiwan Biobank Database (2008-2015), while PM2.5 data were obtained from the Air Quality Monitoring Database (2006-2011).ResultsSmoking and PM2.5 were independently associated with hypomethylation (lower levels) of AHRR cg05575921, AHRR cg23576855, F2RL3 cg03636183, and F2LR3 cg21911711 after multiple-comparison correction (Bonferroni P < 0.00028409). Cg05575921 was the most hypomethylated AHRR CpG site, while cg03636183 was the most hypomethylated F2RL3 CpG site. Overall, cg05575921 was the most hypomethylated CpG site: β = - 0.03909, P < 0.0001; - 0.17536, P < 0.0001 for former and current smoking, respectively (P-trendsmoking < 0.0001) and - 0.00141, P < 0.0001 for PM2.5. After adjusting for F2RL3 cg03636183, smoking and PM2.5 remained significantly associated with cg05575921 hypomethylation: β - 0.02221, P < 0.0001; - 0.11578, P < 0.0001 for former and current smoking, respectively (P-trendsmoking < 0.0001) and - 0.0070, P = 0.0120 for PM2.5. After stratification by sex, smoking and PM2.5 remained associated (P < 0.05) with cg05575921 hypomethylation in both men (β = - 0.04274, - 0.17700, and - 0.00163 for former smoking, current smoking, and PM2.5, respectively) and women (β = - 0.01937, - 0.17255, and - 0.00105 for former smoking, current smoking, and PM2.5, respectively). After stratification by residential area, former and current smoking remained associated (P < 0.05) with cg05575921 hypomethylation: β = - 0.03918 and - 0.17536, respectively (P-trendsmoking < 0.0001). Living in the central and southern areas was also associated (P < 0.05) with cg05575921 hypomethylation: β = - 0.01356 and - 0.01970, respectively (P-trendarea < 0.0001).ConclusionSmoking and PM2.5 were independently associated with hypomethylation of cg05575921, cg23576855, cg03636183, and cg21911711. The most hypomethylated CpG site was cg05575921 and its association with smoking and PM2.5 was dose-dependent.

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Refinement of cg05575921 demethylation response in nascent smoking.

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Refinement of cg05575921 demethylation response in nascent smoking.

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