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Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation.

ABSTRACT: Smoking is a major risk factor in many diseases. Genome wide association studies have linked genes for nicotine dependence and smoking behavior to increased risk of cardiovascular, pulmonary, and malignant diseases. We conducted an epigenome wide association study in peripheral-blood DNA in 464 individuals (22 current smokers and 263 ex-smokers), using the Human Methylation 450 K array. Upon replication in an independent sample of 356 twins (41 current and 104 ex-smokers), we identified 30 probes in 15 distinct loci, all of which reached genome-wide significance in the combined analysis P < 5 × 10(-8). All but one probe (cg17024919) remained significant after adjusting for blood cell counts. We replicated all 9 known loci and found an independent signal at CPOX near GPR15. In addition, we found 6 new loci at PRSS23, AVPR1B, PSEN2, LINC00299, RPS6KA2, and KIAA0087. Most of the lead probes (13 out of 15) associated with cigarette smoking, overlapped regions of open chromatin (FAIRE and DNaseI hypersensitive sites) or/and H3K27Ac peaks (ENCODE data set), which mark regulatory elements. The effect of smoking on DNA methylation was partially reversible upon smoking cessation for longer than 3 months. We report the first statistically significant interaction between a SNP (rs2697768) and cigarette smoking on DNA methylation (cg03329539). We provide evidence that the metSNP for cg03329539 regulates expression of the CHRND gene located circa 95 Kb downstream of the methylation site. Our findings suggest the existence of dynamic, reversible site-specific methylation changes in response to cigarette smoking , which may contribute to the extended health risks associated with cigarette smoking.

SUBMITTER: Tsaprouni LG

PROVIDER: S-EPMC4623553 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation.

Tsaprouni Loukia G LG Yang Tsun-Po TP Bell Jordana J Dick Katherine J KJ Kanoni Stavroula S Nisbet James J Viñuela Ana A Grundberg Elin E Nelson Christopher P CP Meduri Eshwar E Buil Alfonso A Cambien Francois F Hengstenberg Christian C Erdmann Jeanette J Schunkert Heribert H Goodall Alison H AH Ouwehand Willem H WH Dermitzakis Emmanouil E Spector Tim D TD Samani Nilesh J NJ Deloukas Panos P

Epigenetics 20141001 10

Smoking is a major risk factor in many diseases. Genome wide association studies have linked genes for nicotine dependence and smoking behavior to increased risk of cardiovascular, pulmonary, and malignant diseases. We conducted an epigenome wide association study in peripheral-blood DNA in 464 individuals (22 current smokers and 263 ex-smokers), using the Human Methylation 450 K array. Upon replication in an independent sample of 356 twins (41 current and 104 ex-smokers), we identified 30 probe ...[more]

PMID: 25424692

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Project description:ImportanceCigarette smoking during pregnancy increases the risk of preterm birth, low birth weight, and infant mortality.ObjectiveTo assess the probability of preterm birth among expectant mothers who smoked cigarettes before pregnancy and quit smoking at the start or during pregnancy.Design, setting, and participantsThis cross-sectional study analyzed information provided on live birth certificates from 2011 through 2017 that were obtained from US states that implemented the 2003 revision of the US live birth certificate. In total, 25?233?503 expectant mothers who delivered live neonates and had known prepregnancy and trimester-specific cigarette smoking frequency were included in the analyses.ExposuresCigarette smoking frequency (1-9, 10-19, and ?20 cigarettes per day) 3 months prior to pregnancy and for each trimester during pregnancy.Main outcomes and measuresCigarette smoking cessation throughout pregnancy, after the first trimester, after the second trimester, and during the third trimester irrespective of first and second trimester smoking. Probability of preterm birth (<37 weeks' gestation).ResultsOf 25?233?503 expectant mothers who delivered live neonates between 2011 and 2017, the modal age at delivery was 25 to 29 years; 52.9% were non-Hispanic white, 23.6% were Hispanic, and 14.2% were non-Hispanic black women; 22?600?196 mothers did not smoke during the 3 months prior to pregnancy, and 2?633?307 smoked during the 3 months prior to pregnancy. The proportion of prepregnancy smokers who quit throughout pregnancy was 24.3% in 2011 and 24.6% in 2017. The proportion of prepregnancy smokers who quit during the third trimester was 39.5% in 2011 and 39.7% in 2017. High-frequency cigarette smoking often occurred among expectant mothers who smoked during pregnancy (eg, 46.9% of third-trimester smokers smoked ?10 cigarettes per day in 2017). The probability of preterm birth decreased more the earlier smoking cessation occurred in pregnancy. For example, the probability of preterm birth was 9.8% (95% CI, 9.7%-10.0%) among 25- to 29-year-old, non-Hispanic white, primigravida and primiparous expectant mothers (ie, pregnant for the first time and not yet delivered) who smoked 1 to 9 cigarettes per day prior to pregnancy and maintained this frequency throughout their pregnancy. The probability of preterm birth was 9.0% (95% CI, 8.8%-9.1%) if smoking cessation occurred at the start of the second trimester (an 8.9% relative decrease), and 7.8% (95% CI, 7.7%-8.0%) if cessation occurred at the start of pregnancy (a 20.3% relative decrease).Conclusions and relevanceQuitting smoking-and quitting early in pregnancy-was associated with reduced risk of preterm birth even for high-frequency cigarette smokers.

Project description:BackgroundIn the last decade Poland has successfully carried out effective anti-tobacco campaigns and introduced tobacco control legislation. This comprehensive strategy has focused on the general population and has led to a considerable decrease in tobacco consumption. Prisoners constitute a relatively small part of the entire Polish population and smoking habits in this group have been given little attention. The aim of the study was to assess the prevalence of cigarette smoking in Polish male prisoners, factors determining smoking in this group, prisoners' attitudes towards smoking cessation, and to evaluate prisoners' perception of different anti-tobacco measures.MethodsAn anonymous questionnaire including personal, demographic and smoking data was distributed among 944 male inmates. Of these, 907 men aged between 17 and 62 years (mean 32.3 years) met the inclusion criteria of the study. For the comparison of proportions, a chi-square test was used with continuity correction whenever appropriate.ResultsIn the entire group, 81% of the subjects were smokers, 12% - ex-smokers, and 7% - never smokers. Current smokers had significantly lower education level than non-smokers (p < 0.0001) and ever-smokers more frequently abused other psychoactive substances than never smokers (p < 0.0001). Stress was reported as an important factor in prompting smoking (77%). Forty-nine percent of daily smokers were aware of the adverse health consequences of smoking. The majority of smokers (75%) had attempted to quit smoking in the past. Forty percent of smoking prisoners considered an award for abstaining from cigarettes as the best means to limit the prevalence of smoking in prisons.ConclusionThe prevalence of cigarette smoking among Polish prisoners is high. However, a majority of smokers attempt to quit, and they should be encouraged and supported. Efforts to reduce cigarette smoking in prisons need to take into consideration the specific factors influencing smoking habits in prisons.

Dataset Information

Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation.

Publications

Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation.

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