Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy

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.

Download Full-text

The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy

Disease Markers ◽

10.1155/2021/9910878 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Andrea Maugeri ◽

Martina Barchitta ◽

Roberta Magnano San Lio ◽

Giuliana Favara ◽

Claudia La Mastra ◽

...

Keyword(s):

Body Mass Index ◽

Dna Methylation ◽

Body Mass ◽

Methylation Level ◽

Molecular Mechanisms ◽

Smoking Status ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

The Relationship

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.

Download Full-text

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

Genes ◽

10.3390/genes12081276 ◽

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 ◽

...

Keyword(s):

Dna Methylation ◽

Lung Function ◽

Tobacco Smoking ◽

Methylation Level ◽

Smoking Status ◽

Association Studies ◽

Restriction Enzymes ◽

Nicotine Addiction ◽

Cigarette Consumption ◽

Current Tobacco

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).

Download Full-text

Analyses on expression of trimethylation of histone H3 at lysine 27 and DNA methylation at CCGG sites in smoking and nonsmoking non-small cell lung cancer patients and their clinical significance.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23179 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23179-e23179

Author(s):

Xiaohui Chen ◽

Yujie Deng ◽

Kunshou Zhu ◽

Takeshi Nagayasu ◽

Dan Hu ◽

...

Keyword(s):

Lung Cancer ◽

Dna Methylation ◽

Opposite Direction ◽

Methylation Level ◽

Smoking Status ◽

Histone H3 ◽

Small Cell ◽

Small Cell Lung ◽

Ezh2 Expression ◽

Nsclc Patients

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.

Download Full-text

Prenatal Phthalate Exposure Reduction Through an Integrated Intervention Strategy

10.21203/rs.3.rs-280272/v1 ◽

2021 ◽

Author(s):

Wei Wu ◽

Liu Cao ◽

Ting-Ting Zheng ◽

Shu-Yu Feng ◽

Guan-Wei Ma ◽

...

Keyword(s):

Cohort Study ◽

Environmental Factors ◽

Pregnant Women ◽

Phthalate Esters ◽

Intervention Strategy ◽

Urine Samples ◽

Exposure Reduction ◽

Phthalate Exposure ◽

Butyl Phthalate ◽

Subsequent Intervention

Abstract Pregnancy represents a sensitive susceptibility window to phthalate esters (PAEs). In this study, we develop an intervention strategy for reducing the exposure of pregnant women to phthalates. Thirty-five pregnant women, who initially underwent maternity examination, were recruited from an ongoing longitudinal prospective prenatal cohort study. The intervention strategy integrates diet, lifestyle, and environmental factors. Participants were encouraged to modify their behaviors and habits according to the intervention strategy at three different periods. Urine samples were collected from the participants after antenatal examination every month, for 8 months, to measure ten PAEs metabolites. The mono-(2-ethyl-5-hydroxyhexyl) (MEHHP), mono-n-butyl phthalate (MnBP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) declined significantly after the 1st intervention, while mono-isobutyl phthalate (MiBP) and mono-methyl phthalate (MMP) noticeably reduced after 2nd intervention. The sum of the molar concentrations of MEHP, MEHHP, MEOHP, and MECPP reduced by 20% to 40% during subsequent intervention. In addition, the sum of the molar concentrations of MEP, MnBP, MMP, and MiBP) as well as the sum of the molar concentrations of the ten metabolites also reduced. Our findings suggest that intervention through written recommendations can effectively reduce the burden of phthalates during pregnancy.

Download Full-text

DNA methylation of DISC1 gene in schizophrenia using methylight Taqman assay

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v15i1.1261 ◽

2016 ◽

Vol 15 (1) ◽

Author(s):

Nour El Huda Abd Rahim ◽

Mohd Nabil Fikri Rahim ◽

Norsidah Ku Zaifah ◽

Hanisah Mohd Noor ◽

Kartini Abdullah ◽

...

Keyword(s):

Dna Methylation ◽

Methylation Level ◽

Clinical Symptoms ◽

Smoking Status ◽

Methylation Status ◽

Genetic Defect ◽

Taqman Assay ◽

Control Group ◽

Antipsychotic Treatment ◽

Significant Difference

Introduction: Significant evidences from functional studies have shown that DISC1 gene has a role in the pathogenesis of schizophrenia, although the basis of the genetic defect has yet to be established. There has been a shift of emphasis from DISC1 gene variations to other types of genetic defects namely copy number and epigenetic, both of which have not been well investigated. Thus, the aim of this study is to examine the DNA methylation status of DISC1 gene in patients with schizophrenia. Methods: In this study, 239 subjects were included, 117 schizophrenia patients and 122 healthy controls. Genomic DNA was derived from peripheral blood and bisulfite converted. The DNA methylation level was quantitatively measured by Methylight Taqman analysis. Sociodemographic and the clinical parameters were noted. The severity of the clinical symptoms was assessed using Positive and Negative Syndrome Scale (PANSS). Results: The mean age and gender distribution between the study groups were similar. There was no significant difference in the methylation level of DISC1 between the patients and control group. When patients were compared by age, duration of illness, age at diagnosis, body mass index, smoking status, PANSS score and types of antipsychotic treatment, the DNA methylation level of DISC1, did not show any significant difference (p>0.05). Conclusions: This study found no significant difference in methylation level of DISC1 gene between schizophrenia patients and healthy control. Therefore, it is suggested that aberrant DNA methylation of DISC1 most probably does not contribute to the pathogenesis of schizophrenia.

Download Full-text

Determination of Selected Phthalates in Some Commercial Cosmetic Products by HPLC-UV

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200630113850 ◽

2020 ◽

Vol 23 (10) ◽

pp. 1010-1022

Author(s):

Emrah Dural

Keyword(s):

High Performance ◽

Phthalate Esters ◽

High Sensitivity ◽

Hplc Method ◽

Cosmetic Products ◽

Limit Of Quantification ◽

Nail Polish ◽

Accuracy And Precision ◽

Butyl Phthalate

Aim and scope: Due to the serious toxicological risks and their widespread use, quantitative determination of phthalates in cosmetic products have importance for public health. The aim of this study was to develop a validated simple, rapid and reliable high-performance liquid chromatography (HPLC) method for the determination of phthalates which are; dimethyl phthalate (DMP), diethyl phthalate (DEP), benzyl butyl phthalate (BBP), di-n-butyl phthalate (DBP), di(2- ethylhexyl) phthalate (DEHP), in cosmetic products and to investigate these phthalate (PHT) levels in 48 cosmetic products marketing in Sivas, Turkey. Materials and Methods: Separation was achieved by a reverse-phase ACE-5 C18 column (4.6 x 250 mm, 5.0 μm). As the mobile phase, 5 mM KH2PO4 and acetonitrile were used gradiently at 1.5 ml min-1. All PHT esters were detected at 230 nm and the run time was taking 21 minutes. Results: This method showed the high sensitivity value the limit of quantification (LOQ) values for which are below 0.64 μg mL-1 of all phthalates. Method linearity was ≥0.999 (r2). Accuracy and precision values of all phthalates were calculated between (-6.5) and 6.6 (RE%) and ≤6.2 (RSD%), respectively. Average recovery was between 94.8% and 99.6%. Forty-eight samples used for both babies and adults were successfully analyzed by the developed method. Results have shown that, DMP (340.7 μg mL-1 ±323.7), DEP (1852.1 μg mL-1 ± 2192.0), and DBP (691.3 μg mL-1 ± 1378.5) were used highly in nail polish, fragrance and cream products, respectively. Conclusion: Phthalate esters, which are mostly detected in the content of fragrance, cream and nail polish products and our research in general, are DEP (1852.1 μg mL-1 ± 2192.0), DBP (691.3 μg mL-1 ± 1378.5) and DMP (340.7 μg mL-1 ±323.7), respectively. Phthalates were found in the content of all 48 cosmetic products examined, and the most detected phthalates in general average were DEP (581.7 μg mL-1 + 1405.2) with a rate of 79.2%. The unexpectedly high phthalate content in the examined cosmetic products revealed a great risk of these products on human health. The developed method is a simple, sensitive, reliable and economical alternative for the determination of phthalates in the content of cosmetic products, it can be used to identify phthalate esters in different products after some modifications.

Download Full-text

Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

Clinical Epigenetics ◽

10.1186/s13148-021-01004-w ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Pinpin Long ◽

Qiuhong Wang ◽

Yizhi Zhang ◽

Xiaoyan Zhu ◽

Kuai Yu ◽

...

Keyword(s):

Dna Methylation ◽

Acute Coronary Syndrome ◽

Methylation Level ◽

Meta Analysis ◽

Regulation Of Gene Expression ◽

Density Lipoprotein ◽

Blood Leukocytes ◽

Coronary Syndrome ◽

A Genome ◽

Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

Download Full-text

Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults

Toxics ◽

10.3390/toxics9020033 ◽

2021 ◽

Vol 9 (2) ◽

pp. 33

Author(s):

Po-Ching Chu ◽

Charlene Wu ◽

Ta-Chen Su

Keyword(s):

Young Adults ◽

Endothelial Dysfunction ◽

Vascular Diseases ◽

Adolescents And Young Adults ◽

Cardiovascular Risks ◽

Phthalate Exposure ◽

Butyl Phthalate ◽

Microparticle Formation

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.

Download Full-text

The mediating effect of lifestyles on the association between social factors and DNA methylation

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.230 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

A Maugeri ◽

M Barchitta ◽

G Favara ◽

C La Mastra ◽

MC La Rosa ◽

...

Keyword(s):

Physical Activity ◽

Dna Methylation ◽

Socioeconomic Status ◽

Mediterranean Diet ◽

Educational Level ◽

Methylation Level ◽

Mediating Effect ◽

High Educational Level ◽

Age Related ◽

High Educational

Abstract Background Social disadvantage and unhealthy lifestyles may induce molecular changes associated with aging and age-related diseases. For instance, previous studies reported socioeconomic difference in DNA methylation, which in turn led to aberrant gene expression and genome instability. Socioeconomic status (SES) alone, however, does not completely explain this difference, and further studies are needed to unveil what factors contribute to it. Methods We conducted a cross-sectional study on 349 Italian women, aged 25-64 years, to assess SES differences in LINE-1 methylation level - a surrogate marker of global DNA methylation - and to examine the mediating effect of lifestyles (i.e. diet, smoking habits, physical activity, and weight status). Educational level was used as SES indicator. The adherence to Mediterranean diet (MD) was assessed by the Mediterranean Diet Score (MDS). Leukocyte LINE-1 methylation was assessed by pyrosequencing. Mediation analysis was conducted using the PROCESS macro for the SPSS software. Results We first observed that women with high educational level were more likely to be normal weight (p < 0.001) and to adhere to MD (p = 0.018), and less likely to perform physical activity (p = 0.012) than their less educated counterpart. Moreover, age-adjusted linear regression demonstrated that LINE-1 methylation level increased with increasing educational level (β = 0.016; SE = 0.003; p < 0.001). In line, mediation analysis demonstrated an indirect effect of high educational level on LINE-1 methylation through the adherence to MD (β = 0.003; 95%CI=0.001-0.006). Specifically, the mediator could account for 9.5% of the total effect. None of the other lifestyles, instead, exhibited a significant mediating effect. Conclusions To our knowledge, this is the first study demonstrating the mediation of diet in the relationship between SES and DNA methylation. Thus, our findings add even more value to the promotion of healthy dietary habits among social disadvantaged people. Key messages Social disadvantage is associated with epigenetic changes related to aging and age-related diseases. Adherence to the Mediterranean diet might mediate the association between socioeconomic status and DNA methylation.

Download Full-text

DNA methylation mediated RSPO2 to promote follicular development in mammals

Cell Death and Disease ◽

10.1038/s41419-021-03941-z ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Xiaofeng Zhou ◽

Yingting He ◽

Nian Li ◽

Guofeng Bai ◽

Xiangchun Pan ◽

...

Keyword(s):

Dna Methylation ◽

Wnt Signaling ◽

Signaling Pathway ◽

Methylation Level ◽

Molecular Mechanisms ◽

Cpg Island ◽

Wnt Signaling Pathway ◽

Follicular Development ◽

Expression Level

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

Download Full-text