Refinement of cg05575921 demethylation response in nascent smoking

Dawes, Kelsey; Andersen, Allan M.; Papworth, Emma; Hundley, Brandon; Hutchens, Natasha; Manawy, Heba El; Becker, Ashley; Sampson, Luke; Philibert, Willem; Gibbons, Frederick X.; Gerrard, Meg; Philibert, Robert A.

doi:10.1186/s13148-020-00882-w

Cited by 16 publications

(16 citation statements)

References 48 publications

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“…Our methylation levels for cg05575921 were similar to previous reports realized in different populations with tobacco consumption [20,25,32,62,63] and non-smokers [25,63], showing replicable results in most populations studied; this is relevant because, previously, cg05575921 has been proposed as a biomarker of smoking status since DNA methylation is not affected by short-term abstinence periods [32].…”

Section: Discussionsupporting

confidence: 89%

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

Bravo-Gutiérrez

Falfán-Valencia

Ramírez‐Venegas

et al. 2021

Genes

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Tobacco smoking results in a multifactorial disease involving environmental and genetic factors; epigenome-wide association studies (EWAS) show changes in DNA methylation levels due to cigarette consumption, partially reversible upon tobacco smoking cessation. Therefore, methylation levels could predict smoking status. This study aimed to evaluate the DNA methylation level of cg05575921 (AHRR) and cg23771366 (PRSS23) and their correlation with lung function variables, cigarette consumption, and nicotine addiction in the Mexican smoking population. We included 114 non-smokers (NS) and 102 current tobacco smokers (TS); we then further subclassified them as heavy smokers (HS) (n = 53) and light smokers (LS) (n = 49). We used restriction enzymes (MspI/HpaII) and qPCR to determine the DNA methylation level. We observed significant hypomethylation of cg05575921 in smokers compared to NS (p = 0.003); further analysis found a difference between HS and NS (p = 0.02). We did not observe differences between other groups or a positive correlation between methylation levels and age, BMI, cigarette consumption, nicotine addiction, or lung function. In conclusion, the cg05575921 site of AHRR is significantly hypomethylated in Mexican smokers, especially in HS (≥20 cigarettes per day).

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Section: Discussionsupporting

confidence: 89%

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

Bravo-Gutiérrez

Falfán-Valencia

Ramírez‐Venegas

et al. 2021

Genes

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“…In that study, on the presumption that most high school sophomores will not yet have started smoking, we enrolled 15 year-old high school students and followed them for two years, drawing their blood and measuring their CO levels at three points of time. In the 364 subjects who denied any type of smoking and had negative cotinine and cannabinoid levels, the average level of cg05575921 methylation at age 15 using this assay was 86.8% ± 3.2 22 . That is very similar to the 86.6% ± 2.9 found in these 423 biochemically screened adults and strongly argues against any significant age dependent changes in cg05575921 methylation in adult subjects.…”

Section: Discussionmentioning

confidence: 95%

“…To address these challenges and establish the methylation set points of cg05575921 methylation, we have surveyed populations with low likelihood of significant underreporting to get a better understanding of the assay set point in various groups. The most notable effort prior to this communication has been the Healthy Iowan Study 22 . In that study, on the presumption that most high school sophomores will not yet have started smoking, we enrolled 15 year-old high school students and followed them for two years, drawing their blood and measuring their CO levels at three points of time.…”

Section: Discussionmentioning

confidence: 99%

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

Dawes

Andersen

Reimer

et al. 2021

Sci Rep

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Numerous studies have shown that cg05575921 methylation decreases in response to smoking. However, secondary to methodological issues, the magnitude and dose dependency of that response is as of yet unclear. This lack of certainty is a barrier to the use of DNA methylation clinically to assess and monitor smoking status. To better define this relationship, we conducted a joint analysis of methylation sensitive PCR digital (MSdPCR) assessments of cg05575921 methylation in whole blood and/or saliva DNA to smoking using samples from 421 smokers and 423 biochemically confirmed non-smokers from 4 previously published studies. We found that cg05575921 methylation manifested a curvilinear dose dependent decrease in response to increasing cigarette consumption. In whole blood DNA, the Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) of cg05575921 methylation for predicting daily smoking status was 0.98. In saliva DNA, the gross AUC was 0.91 with correction for cellular heterogeneity improving the AUC to 0.94. Methylation status was significantly associated with the Fagerstrom Test for Nicotine Dependence score, but with significant sampling heterogeneity. We conclude that MSdPCR assessments of cg05575921 methylation are a potentially powerful, clinically implementable tool for the assessment and management of smoking.

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“…Recent advances in the field of epigenetics may offer a means of overcoming some limitations of current smoking biomarkers. In particular, multiple studies and meta-analyses ( 27 , 32 , 33 ) have shown that decreased methylation of the genomic CpG cg05575921, located in the gene Aryl Hydrocarbon Receptor Repressor ( AHRR ), is a strongly performing biomarker for cigarette (AUC = 0.99) ( 34 ) that is both sensitive to light smoking ( 35 ) and demonstrate dose-response characteristics ( 34 , 36 , 37 ).…”

Section: Introductionmentioning

confidence: 99%

An Examination of Risk Factors for Tobacco and Cannabis Smoke Exposure in Adolescents Using an Epigenetic Biomarker

et al. 2021

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Objective: Evolving patterns of nicotine and cannabis use by adolescents require new tools to understand the changing epidemiology of these substances. Here we describe the use of a novel epigenetic biomarker sensitive to both tobacco and cannabis smoke in a longitudinal sample of high-risk adolescents. We examine risk factors for positivity for this epigenetic biomarker in comparison to positivity for conventional serum biomarkers of nicotine and cannabis use.Method: Eastern Iowa 10th graders who had a friend or family member who smoked were eligible to participate in a longitudinal study over 10–12th grades. Subjects provided self-report data on nicotine, tobacco, and cannabis use patterns as well as blood samples that were used for serum cotinine and THC assays. DNA was prepared for analysis of methylation at the CpG cg05575921, a sensitive indicator of smoke exposure. Relationships between positivity for each these biomarkers and a variety of risk factors, including demographics, family and peer relationships, psychopathology, willingness to smoke, and perceptions of typical cigarette and cannabis users, were examined at the 10th (n = 442), 11th (n = 376), and 12th (n = 366) grade timepoints.Results: A increasing proportion of subjects were positive for cotinine (5–16%), THC (3–10%), and cg05575921 methylation (5–7%) across timepoints, with some overlap. Self-reported combusted tobacco and cannabis use was strongly correlated with all biomarkers, whereas cg05575921 methylation was not correlated with reported e-cigarette use. Dual users, defined as those positive for nicotine and THC in the 12th grade showed the greatest cumulative smoke exposure, indicated by cg05575921 methylation. Subjects reported more positive attitudes toward cannabis users than cigarette smokers, and willingness to smoke and positive perceptions of tobacco and cannabis smokers were significant risk factors for biomarker positivity across timepoints.Conclusion: We conclude that measurement of cg05575921 methylation in adolescents is a useful tool in detecting tobacco smoking in adolescents, and may be a novel tool for the detection of cannabis smoking and cannabis and tobacco co-use, though non-combusted forms of nicotine use do not appear to be detectable by this method.

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Refinement of cg05575921 demethylation response in nascent smoking

Cited by 16 publications

References 48 publications

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

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

An Examination of Risk Factors for Tobacco and Cannabis Smoke Exposure in Adolescents Using an Epigenetic Biomarker

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