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

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1276
Author(s):  
Omar Andrés Bravo-Gutiérrez ◽  
Ramcés Falfán-Valencia ◽  
Alejandra Ramírez-Venegas ◽  
Raúl H. Sansores ◽  
Rafael de Jesús Hernández-Zenteno ◽  
...  

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).

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wan-Ru Wang ◽  
Nai-Tzu Chen ◽  
Nai-Yun Hsu ◽  
I-Ying Kuo ◽  
Hsin-Wen Chang ◽  
...  

Abstract Background Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases. Results Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children’s respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (β =  − 1.75, p = 0.015) after adjustment for child’s sex, age, BMI, parents’ smoking status, allergic history, and education levels, PM2.5, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65–0.99). Conclusions Exposure to BBzP in settled dust might increase children’s respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Giuliana Favara ◽  
Claudia La Mastra ◽  
...  

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.


Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
James S Pankow ◽  
Ellen W Demerath ◽  
Weihua Guan ◽  
Myriam Fornage ◽  
Thomas H Mosley ◽  
...  

DNA methylation is mitotically heritable modification in chromatin structure that impacts transcriptional control of genes and cellular function. Recent technological advances provide opportunities to systematically interrogate variation in DNA methylation across the genome in large epidemiologic studies. However, unlike inherited changes to the genetic sequence, variation in site-specific methylation varies by tissue, stage of development, disease state, and may be affected by gender, aging and exposure to environmental factors. As a result, there is likely a greater threat of confounding in epigenome-wide methylation studies compared to genome-wide association studies of SNPs. The Illumina Infinium HumanMethylation450 BeadChip was used to measure DNA methylation in peripheral blood obtained from African American participants from the Jackson, Mississippi and Forsyth County, North Carolina field centers of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort of middle-aged men and women. After excluding outlier samples and CpG sites using quality control filters, we analyzed 473,687 sites in 2873 subjects who were between 47-71 years of age at the time of DNA collection. We used linear regression with robust standard errors to examine cross-sectional associations of demographic factors with the beta value, an estimate of the average methylation level at each locus, and applied a Bonferroni correction to account for multiple testing. In univariate analysis, 91% of sites on the X chromosome and 10% of sites on the autosomes exhibited statistically significant gender differences in methylation level (p<1x10-7). Average methylation was higher in women than men for most of the significant sites (63% and 89% on the X chromosome and autosomes, respectively). Percent European ancestry estimated from ancestry informative markers was significantly associated with methylation level at 4% of sites. Age was also significantly associated with methylation at 4% of sites; average methylation was lower in older subjects compared to younger subjects for the majority (58%) of these sites. As we begin to implement epigenome-wide studies of DNA methylation and CVD outcomes, these results indicate that such studies will require careful consideration of adjustment techniques to avoid confounding by gender, age, and other covariates.


Author(s):  
Nicholas S Hopkinson ◽  
Niccolo Rossi ◽  
Julia El-Sayed Moustafa ◽  
Anthony A Laverty ◽  
Jennifer K Quint ◽  
...  

Background: The association between current tobacco smoking, the risk of developing COVID-19 and the severity of illness is an important information gap. Methods: UK users of the COVID Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, were asked to log symptoms daily from 24th March 2020 to 23rd April 2020. Participants reporting that they did not feel physically normal were taken through a series of questions, including 14 potential COVID-19 symptoms and any hospital attendance. The main study outcome was the association between current smoking and the development of classic symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness. The number of concurrent COVID-19 symptoms was used as a proxy for severity. In addition, association of subcutaneous adipose tissue expression of ACE2, both the receptor for SARS-CoV-2 and a potential mediator of disease severity, with smoking status was assessed in a subset of 541 twins from the TwinsUK cohort. Results: Data were available on 2,401,982 participants, mean(SD) age 43.6(15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834,437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to develop symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR[95%CI] 1.14[1.10 to 1.18]; >5 symptoms 1.29[1.26 to 1.31]; >10 symptoms 1.50[1.42 to 1.58]. Smoking was associated with reduced ACE2 expression in adipose tissue (Beta(SE)= -0.395(0.149); p=7.01x10-3). Interpretation: These data are consistent with smokers having an increased risk from COVID-19.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216422
Author(s):  
Nicholas S Hopkinson ◽  
Niccolo Rossi ◽  
Julia El-Sayed_Moustafa ◽  
Anthony A Laverty ◽  
Jennifer K Quint ◽  
...  

BackgroundThe association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap.MethodsUK users of the Zoe COVID-19 Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance. The main study outcome was the development of ‘classic’ symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness and their association with current smoking. The number of concurrent COVID-19 symptoms was used as a proxy for severity and the pattern of association between symptoms was also compared between smokers and non-smokers.ResultsBetween 24 March 2020 and 23 April 2020, data were available on 2 401 982 participants, mean (SD) age 43.6 (15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834 437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to report symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR (95% CI) 1.14 (1.10 to 1.18); >5 symptoms 1.29 (1.26 to 1.31); >10 symptoms 1.50 (1.42 to 1.58). The pattern of association between reported symptoms did not vary between smokers and non-smokers.InterpretationThese data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19.


Author(s):  
Babatunde O. A. Adegoke ◽  
Ayodele Akintunde AKINREMI ◽  
Adekemi E Akintobi

Background: Tobacco smoking is a risk factor for chronic respiratory disorders. The tobacco epidemic is driven by adolescents and young adults. Tobacco-related morbidity rises with increasing years of smoking, and the increasing number of young smokers may have considerable future public health implications.Objective: This study investigated the effect of tobacco smoking on pulmonary function indices among undergraduate students. Methods: This is a cross sectional study involving 104 male undergraduate students between 18 and 30 years of age. They were recruited by snowball sampling and were grouped based on their smoking status (current smoker 52: non-smoker 52). Participants with signs of respiratory disease, thoracic spine deformity, or contraindication to spirometry were excluded from the study. Participants’ forced vital capacity (FVC), forced expiratory volume in first second (FEV1), both in litres, and forced expiratory ratio (FER) in percentage were assessed using standard protocols. Data were analyzed using mean, standard deviation, independent t-test and chi-square test with alpha level set at 0.05.Results: The two groups were not significantly different in age, height and body mass index (BMI). Smokers had significantly reduced FVC (3.42±0.42 vs 3.87±0.4 litres) p=0.03; FEV1 (2.39±0.37 vs 3.22±0.38 litres) p=0.001 and FER (%) (70.7±7.58vs82.3±4.05) p=0.01. Among the smokers, a relationship was observed between years and numbers of cigarettes smoked and lung function. The proportion of participants with FER below the age-matched reference was significantly higher among smokers than non-smokers (40.4%vs6.7%) at p=0.021. Conclusion: Smoking reduced pulmonary function among undergraduate students. This may have important public health implications since continued smoking may accelerate lung function deterioration and consequently increase the future risk of developing lung disease.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23179-e23179
Author(s):  
Xiaohui Chen ◽  
Yujie Deng ◽  
Kunshou Zhu ◽  
Takeshi Nagayasu ◽  
Dan Hu ◽  
...  

e23179 Background: Smoking usually leads to epigenetic alterations like DNA methylation and histone modifications. We analyzed the effect that smoking had on DNA methylation level at CCGG sites and expression of trimethylation of histone H3 lysine 27 (H3K27me3), enhancer of zeste homolog 2 (EZH2) and their interactions in non-small cell lung cancer (NSCLC) patients. Methods: 42 NSCLC patients, 22 adenocarcinomas and 20 squamous cell carcinomas were enrolled. Expression of H3K27me3, EZH2 and PCNA were immunohistochemically detected. Apoptotic index in NSCLC with different smoking status was evaluated via TUNEL method. DNA methylation at CCGG sites was evaluated by HELMET method. Their correlation with clinicopathological data were calculated in relation to different smoking status. Results: Compared to the nonsmokers, smoker NSCLC patients were found more often of lower level of DNA methylation at CCGG sites, lower H3K27me3 expression and higher EZH2 expression, and lower apoptotic cell index ( P< 0.05). DNA methylation level at CCGG sites negatively correlated to the Binkman Index( P= 0.017). Further, trend of H3K27me3 and EZH2 expression was in the same direction in most smokers, while in nonsmokers, their expression trend was mostly in the opposite direction ( P= 0.015). Trend of PCNA and EZH2 expression was in the opposite direction in most smokers, while in nonsmokers, their expression trend was mostly in the same direction ( P= 0.048). In addition, trend of CCGG methylation ratio and immunohistochemical expression of H3K27me3 was in the same direction in most smokers, while in nonsmokers, the trend was mostly in the opposite direction ( P= 0.049). Conclusions: NSCLC patients of different smoking status exhibit completely different epigenetic characteristics, and DNA methylation at CCGG sites would probably determine the expression trend of H3K27me3, EZH2 and PCNA.


Author(s):  
Angelica Tiotiu ◽  
Iulia Ioan ◽  
Nathalie Wirth ◽  
Rodrigo Romero-Fernandez ◽  
Francisco-Javier González-Barcala

Background: Tobacco smoking is associated with more severe asthma symptoms, an accelerated decline in lung function, and reduced responses to corticosteroids. Our objective was to compare asthma outcomes in terms of disease control, exacerbation rates, and lung function in a population of asthmatic patients according to their smoking status. Methods: We compared patients’ demographics, disease characteristics, and lung-function parameters in current-smokers (CS, n = 48), former-smokers (FS, n = 38), and never-smokers (NS, n = 90), and identified predictive factors for asthma control. Results: CS had a higher prevalence of family asthma/atopy, a lower rate of controlled asthma, impaired perception of dyspnea, an increased number of exacerbations, and poorer lung function compared to NS. The mean asthma control questionnaire’s (ACQ) score was higher in CS vs. NS and FS (1.9 vs. 1.2, p = 0.02). Compared to CS, FS had a lower rate of exacerbations, a better ACQ score (similar to NS), a higher prevalence of dyspnea, and greater lung-diffusion capacity. Non-smoking status, the absence of dyspnea and exacerbations, and a forced expiratory volume in one second ≥80% of predicted were associated with controlled asthma. Conclusions: CS with asthma exhibit worse clinical and functional respiratory outcomes compared to NS and FS, supporting the importance of smoking cessation in this population.


2021 ◽  
Vol 12 ◽  
Author(s):  
Veronika V. Odintsova ◽  
Valerie Rebattu ◽  
Fiona A. Hagenbeek ◽  
René Pool ◽  
Jeffrey J. Beck ◽  
...  

We examined the performance of methylation scores (MS) and polygenic scores (PGS) for birth weight, BMI, prenatal maternal smoking exposure, and smoking status to assess the extent to which MS could predict these traits and exposures over and above the PGS in a multi-omics prediction model. MS may be seen as the epigenetic equivalent of PGS, but because of their dynamic nature and sensitivity of non-genetic exposures may add to complex trait prediction independently of PGS. MS and PGS were calculated based on genotype data and DNA-methylation data in blood samples from adults (Illumina 450 K; N = 2,431; mean age 35.6) and in buccal samples from children (Illumina EPIC; N = 1,128; mean age 9.6) from the Netherlands Twin Register. Weights to construct the scores were obtained from results of large epigenome-wide association studies (EWASs) based on whole blood or cord blood methylation data and genome-wide association studies (GWASs). In adults, MSs in blood predicted independently from PGSs, and outperformed PGSs for BMI, prenatal maternal smoking, and smoking status, but not for birth weight. The largest amount of variance explained by the multi-omics prediction model was for current vs. never smoking (54.6%) of which 54.4% was captured by the MS. The two predictors captured 16% of former vs. never smoking initiation variance (MS:15.5%, PGS: 0.5%), 17.7% of prenatal maternal smoking variance (MS:16.9%, PGS: 0.8%), 11.9% of BMI variance (MS: 6.4%, PGS 5.5%), and 1.9% of birth weight variance (MS: 0.4%, PGS: 1.5%). In children, MSs in buccal samples did not show independent predictive value. The largest amount of variance explained by the two predictors was for prenatal maternal smoking (2.6%), where the MSs contributed 1.5%. These results demonstrate that blood DNA MS in adults explain substantial variance in current smoking, large variance in former smoking, prenatal smoking, and BMI, but not in birth weight. Buccal cell DNA methylation scores have lower predictive value, which could be due to different tissues in the EWAS discovery studies and target sample, as well as to different ages. This study illustrates the value of combining polygenic scores with information from methylation data for complex traits and exposure prediction.


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