Epigenetics Insights最新文献

{"title":"Exploring the Ethics of Implementation of Epigenomics Technologies in Cancer Screening: A Focus Group Study.","authors":"Eline M Bunnik,&nbsp;Ineke Lle Bolt","doi":"10.1177/25168657211063618","DOIUrl":"https://doi.org/10.1177/25168657211063618","url":null,"abstract":"<p><p>New epigenomics technologies are being developed and used for the detection and prediction of various types of cancer. By allowing for timely intervention or preventive measures, epigenomics technologies show promise for public health, notably in population screening. In order to assess whether implementation of epigenomics technologies in population screening may be morally acceptable, it is important to understand - in an early stage of development - ethical and societal issues that may arise. We held 3 focus groups with experts in science and technology studies (STS) (n = 13) in the Netherlands, on 3 potential future applications of epigenomic technologies in screening programmes of increasing scope: cervical cancer, female cancers and 'global' cancer. On the basis of these discussions, this paper identifies ethical issues pertinent to epigenomics-based population screening, such as risk communication, trust and public acceptance; personal responsibility, stigmatisation and societal pressure, and data protection and data governance. It also points out how features of epigenomics (eg, modifiability) and changing concepts (eg, of cancer) may challenge the existing evaluative framework for screening programmes. This paper aims to anticipate and prepare for future ethical challenges when epigenomics technologies can be tested and introduced in public health settings.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211063618"},"PeriodicalIF":2.2,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39822233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Histone H3 Lysine 4 Trimethylation (H3K4me3) Landscape Changes in Response to TGFβ.","authors":"Ankit Naik,&nbsp;Nidhi Dalpatraj,&nbsp;Noopur Thakur","doi":"10.1177/25168657211051755","DOIUrl":"https://doi.org/10.1177/25168657211051755","url":null,"abstract":"<p><p>TGFβ expression acts as a biomarker of poor prognosis in prostate cancer. It plays a dual functional role in prostate cancer. In the early stages of the tumor, it acts as a tumor suppressor while at the later stages of tumor development, it promotes metastasis. The molecular mechanisms of action of TGFβ are largely understood through the canonical and non-canonical signal transduction pathways. Our understanding of the mechanisms that establish transient TGFβ stimulation into stable gene expression patterns remains incomplete. Epigenetic marks like histone H3 modifications are directly linked with gene expression and they play an important role in tumorigenesis. In this report, we performed chromatin immunoprecipitation-sequencing (ChIP-Seq) to identify the genome-wide regions that undergo changes in histone H3 Lysine 4 trimethylation (H3K4me3) occupancy in response to TGFβ stimulation. We also show that TGFβ stimulation can induce acute epigenetic changes through the modulation of H3K4me3 signals at genes belonging to special functional categories in prostate cancer. TGFβ induces the H3K4me3 on its own ligands like TGFβ, GDF1, INHBB, GDF3, GDF6, BMP5 suggesting a positive feedback loop. The majority of genes were found to be involved in the positive regulation of transcription from the RNA polymerase II promoter in response to TGFβ. Other functional categories were intracellular protein transport, brain development, EMT, angiogenesis, antigen processing, antigen presentation via MHC class II, lipid transport, embryo development, histone H4 acetylation, positive regulation of cell cycle arrest, and genes involved in mitotic G2 DNA damage checkpoints. Our results link TGFβ stimulation to acute changes in gene expression through an epigenetic mechanism. These findings have broader implications on epigenetic bases of acute gene expression changes caused by growth factor stimulation.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211051755"},"PeriodicalIF":2.2,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/e3/10.1177_25168657211051755.PMC8521735.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39535652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Asthma and Rhinitis with Epigenetics of Coronavirus Related Genes.","authors":"Aniruddha Rathod,&nbsp;Rutu Rathod,&nbsp;Hongmei Zhang,&nbsp;Parnian Kheirkhah Rahimabad,&nbsp;Wilfried Karmaus,&nbsp;Hasan Arshad","doi":"10.1177/25168657211039224","DOIUrl":"https://doi.org/10.1177/25168657211039224","url":null,"abstract":"<p><strong>Introduction: </strong>Susceptibility factors for coronavirus disease 2019 (COVID-19) include sex and medical conditions such as asthma and rhinitis. DNA methylation (DNAm) is associated with asthma, rhinitis, and several viruses. We examined associations of asthma/rhinitis with DNAm at CpGs located on coronavirus related genes, and if these associations were sex-specific.</p><p><strong>Methods: </strong>In total, n = 242 subjects aged 26 years from the Isle of Wight Birth Cohort were included in the study. Linear regressions were used to examine sex specific and non-specific associations of DNAm at CpGs on coronavirus related genes with asthma/rhinitis status. Associations of DNAm with gene expression in blood were assessed for functional relevance of identified CpGs.</p><p><strong>Results: </strong>Statistically significant interaction effects of asthma or rhinitis with sex were identified at 40 CpGs for asthma and 27 CpGs for rhinitis. At 21 CpGs, DNAm was associated with asthma, and at 45 CpGs with rhinitis, regardless of sex. Assessment of functional relevance of the identified CpGs indicated a potential of epigenetic regulatory functionality on gene activity at 14 CpGs for asthma and 17 CpGs for rhinitis, and of those 6 CpGs for asthma and 7 CpGs for rhinitis were likely to be sex-specific.</p><p><strong>Conclusion: </strong>Subjects with asthma/rhinitis may have altered susceptibility to COVID-19 due to changes in their DNAm associated with these conditions. Sex specificity on association of asthma/rhinitis with DNAm at certain CpGs, and on the association of DNAm at asthma/rhinitis-linked CpGs with gene expression have the potential to explain the reported sex-specificity in COVID-19 morbidity and mortality.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211039224"},"PeriodicalIF":2.2,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/a4/10.1177_25168657211039224.PMC8485269.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39484589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation at Birth is Associated with Childhood Serum Immunoglobulin E Levels.","authors":"Luhang Han, Akhilesh Kaushal, Hongmei Zhang, Latha Kadalayil, Jiasong Duan, John W Holloway, Wilfried Karmaus, Pratik Banerjee, Shih-Fen Tsai, Hui-Ju Wen, Syed Hasan Arshad, Shu-Li Wang","doi":"10.1177/25168657211008108","DOIUrl":"10.1177/25168657211008108","url":null,"abstract":"<p><p>Immunoglobulin E (IgE) is known to play an important role in allergic diseases. Epigenetic traits acquired due to modification of deoxyribonucleic acid (DNA) methylation (DNAm) in early life may have phenotypic consequences through their role in transcriptional regulation with relevance to the developmental origins of diseases including allergy. However, epigenome-scale studies on the longitudinal association of cord blood DNAm with IgE over time are lacking. Our study aimed to examine the association of DNAm at birth with childhood serum IgE levels during early life. Genome-scale DNAm and total serum IgE measured at birth, 5, 8, and 11 years of children in the Taiwan Maternal and Infant Cohort Study were included in the study in the discovery stage. Linear mixed models were implemented to assess the association between cord blood DNAm at ~310K 5'-cytosine-phosphate-guanine-3' (CpG) sites with repeated IgE measurements, adjusting for cord blood IgE. Identified statistically significant CpGs (at a false discovery rate, FDR, of 0.05) were further tested in an independent replication cohort, the Isle of Wight (IoW) birth cohort. We mapped replicated CpGs to genes and conducted gene ontology analysis using ToppFun to identify significantly enriched pathways and biological processes of the genes. Cord blood DNAm of 273 CpG sites were significantly (FDR = 0.05) associated with IgE levels longitudinally. Among the identified CpGs available in both cohorts (184 CpGs), 92 CpGs (50%) were replicated in the IoW in terms of consistency in direction of associations between DNA methylation and IgE levels later in life, and 16 of the 92 CpGs showed statistically significant associations (<i>P</i> < .05). Gene ontology analysis identified 4 pathways (FDR = 0.05). The identified 16 CpG sites had the potential to serve as epigenetic markers associated with later IgE production, beneficial to allergic disease prevention and intervention.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211008108"},"PeriodicalIF":3.6,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e1/fb/10.1177_25168657211008108.PMC8024453.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38819612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships among Inorganic Arsenic, Nutritional Status CpG Methylation and microRNAs: A Review of the Literature.","authors":"Abhishek Venkatratnam,&nbsp;Carmen A Marable,&nbsp;Arjun M Keshava,&nbsp;Rebecca C Fry","doi":"10.1177/2516865721989719","DOIUrl":"https://doi.org/10.1177/2516865721989719","url":null,"abstract":"<p><p>Inorganic arsenic is a naturally occurring toxicant that poses a significant and persistent challenge to public health. The World Health Organization has identified many geographical regions where inorganic arsenic levels exceed safe limits in drinking water. Numerous epidemiological studies have associated exposure to inorganic arsenic with increased risk of adverse health outcomes. Randomized clinical trials have shown that nutritional supplementation can mitigate or reduce exacerbation of exposure-related effects. Although a growing body of evidence suggests that epigenetic status influences toxicity, the relationships among environmental exposure to arsenic, nutrition, and the epigenome are not well detailed. This review provides a comprehensive summary of findings from human, rodent, and in vitro studies highlighting these interactive relationships.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865721989719"},"PeriodicalIF":2.2,"publicationDate":"2021-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865721989719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25391949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States.","authors":"Jaclyn M Goodrich,&nbsp;Melissa A Furlong,&nbsp;Alberto J Caban-Martinez,&nbsp;Alesia M Jung,&nbsp;Ken Batai,&nbsp;Timothy Jenkins,&nbsp;Shawn Beitel,&nbsp;Sally Littau,&nbsp;John Gulotta,&nbsp;Darin Wallentine,&nbsp;Jeff Hughes,&nbsp;Charles Popp,&nbsp;Miriam M Calkins,&nbsp;Jefferey L Burgess","doi":"10.1177/25168657211006159","DOIUrl":"https://doi.org/10.1177/25168657211006159","url":null,"abstract":"<p><p>Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw <i>P</i>-value <.05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate (<i>q</i>-value <.05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at <i>q</i> < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene <i>SULT1C2</i> had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies (<i>FOXK2, GYLTL1B, ZBTB16, ARHGEF10</i>, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"14 ","pages":"25168657211006159"},"PeriodicalIF":2.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/25168657211006159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10768648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort.","authors":"Jaclyn M Goodrich, Emily C Hector, Lu Tang, Jennifer L LaBarre, Dana C Dolinoy, Adriana Mercado-Garcia, Alejandra Cantoral, Peter Xk Song, Martha Maria Téllez-Rojo, Karen E Peterson","doi":"10.1177/2516865720977888","DOIUrl":"10.1177/2516865720977888","url":null,"abstract":"<p><p>Epigenetic modifications, such as DNA methylation, influence gene expression and cardiometabolic phenotypes that are manifest in developmental periods in later life, including adolescence. Untargeted metabolomics analysis provide a comprehensive snapshot of physiological processes and metabolism and have been related to DNA methylation in adults, offering insights into the regulatory networks that influence cellular processes. We analyzed the cross-sectional correlation of blood leukocyte DNA methylation with 3758 serum metabolite features (574 of which are identifiable) in 238 children (ages 8-14 years) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Associations between these features and percent DNA methylation in adolescent blood leukocytes at LINE-1 repetitive elements and genes that regulate early life growth (<i>IGF2, H19, HSD11B2</i>) were assessed by mixed effects models, adjusting for sex, age, and puberty status. After false discovery rate correction (FDR <i>q</i> < 0.05), 76 metabolites were significantly associated with LINE-1 DNA methylation, 27 with <i>HSD11B2</i>, 103 with <i>H19</i>, and 4 with <i>IGF2</i>. The ten identifiable metabolites included dicarboxylic fatty acids (five associated with LINE-1 or <i>H19</i> methylation at <i>q</i> < 0.05) and 1-octadecanoyl-rac-glycerol (<i>q</i> < 0.0001 for association with <i>H19</i> and <i>q</i> = 0.04 for association with LINE-1). We then assessed the association between these ten known metabolites and adiposity 3 years later. Two metabolites, dicarboxylic fatty acid 17:3 and 5-oxo-7-octenoic acid, were inversely associated with measures of adiposity (<i>P</i> < .05) assessed approximately 3 years later in adolescence. In stratified analyses, sex-specific and puberty-stage specific (Tanner stage = 2 to 5 vs Tanner stage = 1) associations were observed. Most notably, hundreds of statistically significant associations were observed between <i>H19</i> and LINE-1 DNA methylation and metabolites among children who had initiated puberty. Understanding relationships between subclinical molecular biomarkers (DNA methylation and metabolites) may increase our understanding of genes and biological pathways contributing to metabolic changes that underlie the development of adiposity during adolescence.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"13 ","pages":"2516865720977888"},"PeriodicalIF":4.8,"publicationDate":"2020-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/c8/10.1177_2516865720977888.PMC7734565.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy.","authors":"Sultan Abda Neja","doi":"10.1177/2516865720964808","DOIUrl":"https://doi.org/10.1177/2516865720964808","url":null,"abstract":"<p><p>Aberrant promoter DNA hypermethylation is a typical characteristic of cancer and it is often seen in malignancies. Recent studies showed that regulatory cis-elements found up-stream of many tumor suppressor gene promoter CpG island (CGI) attract DNA methyltransferases (DNMT) that hypermethylates and silence the genes. As epigenetic alterations are potentially reversible, they make attractive targets for therapeutic intervention. The currently used decitabine (DAC) and azacitidine (AZA) are DNMT inhibitors that follow the passive demethylation pathway. However, they lead to genome-wide demethylation of CpGs in cells, which makes difficult to use it for causal effect analysis and treatment of specific epimutations. Demethylation through specific demethylase enzymes is thus critical for epigenetic resetting of silenced genes and modified chromatins. Yet DNA-binding factors likely play a major role to guide the candidate demethylase enzymes upon its fusion. Before the advent of clustered regulatory interspaced short palindromic repeats (CRISPR), both zinc finger proteins (ZNFs) and transcription activator-like effector protein (TALEs) were used as binding platforms for ten-eleven translocation (TET) enzymes and both systems were able to induce transcription at targeted loci in an <i>in vitro</i> as well as <i>in vivo</i> model. Consequently, the development of site-specific and active demethylation molecular trackers becomes more than hypothetical to makes a big difference in the treatment of cancer in the future. This review is thus to recap the novel albeit distinct studies on the potential use of site-specific demethylation for the development of epigenetic based cancer therapy.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720964808"},"PeriodicalIF":2.2,"publicationDate":"2020-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720964808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39827856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>E-Cadherin, NFATC3</i>, and <i>PLP2</i> Are Differentially Methylated in Multiple Cancers.","authors":"Mary J Lotesto,&nbsp;Christopher J Wallace,&nbsp;Stacey L Raimondi","doi":"10.1177/2516865720964802","DOIUrl":"https://doi.org/10.1177/2516865720964802","url":null,"abstract":"<p><p>It is well documented that cancer cells have abnormal methylation patterns often caused by faulty methylating machinery. Specifically, <i>E-cadherin, NFATC3</i>, and <i>PLP2</i> are 3 genes known to be aberrantly methylated in cancer cells. These genes are well documented for their role in signaling pathways involved with cell proliferation, adhesion, migration, and other signs of tumor progression. Therefore, changes in gene expression of <i>CDH1, NFATC3</i>, and <i>PLP2</i> due to aberrant methylation can lead to profound changes in cellular function and tumor formation. In order to ensure that previous <i>in vitro</i> and <i>in vivo</i> methylation studies match what is observed in the clinic, we utilized a bioinformatics approach to complete an extensive analysis of methylation patterns of these 3 genes, analyzing over 5000 patient samples, across all cancers for which both normal and tumor tissues were available. Specifically, we analyzed overall and site-specific methylation patterns, at CpG islands and shores, of all 3 genes across 14 cancer types. Furthermore, we compared these methylation levels in normal and tumor samples of both matched and unmatched patient samples in order to determine any differences between groups. Finally, we examined whether an aberrant DNA methyltransferase, <i>DNMT3B7</i>, known to be expressed in cancer cells and to alter methylation patterns <i>in vitro</i> correlated with altered overall and site-specific methylation of <i>CDH1, NFATC3</i>, and <i>PLP2</i> in these patient samples. Our results indicate that methylation patterns of <i>CDH1</i> and <i>NFATC3</i> were unexpectedly varied across tumors, contrary to previous studies performed <i>in vitro</i>, while <i>PLP2</i> showed the expected hypomethylation pattern in tumor tissues. We also observed some correlation between <i>DNMT3B7</i> expression and methylation patterns of these genes, but patterns were inconsistent. Taken together, these results emphasize the necessity for <i>in vivo</i> and patient studies rather than a complete reliance on <i>in vitro</i> data and provide multiple areas of future research.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720964802"},"PeriodicalIF":2.2,"publicationDate":"2020-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720964802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38593823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation of Endoglin Pathway Genes in Pregnant Women With and Without Preeclampsia.","authors":"Allison H Rietze,&nbsp;Yvette P Conley,&nbsp;Dianxu Ren,&nbsp;Cindy M Anderson,&nbsp;James M Roberts,&nbsp;Arun Jeyabalan,&nbsp;Carl A Hubel,&nbsp;Mandy J Schmella","doi":"10.1177/2516865720959682","DOIUrl":"https://doi.org/10.1177/2516865720959682","url":null,"abstract":"<p><strong>Objective: </strong>We compared blood-based DNA methylation levels of endoglin (<i>ENG</i>) and transforming growth factor beta receptor 2 (<i>TGFβR2</i>) gene promoter regions between women with clinically-overt preeclampsia and women with uncomplicated, normotensive pregnancies.</p><p><strong>Methods: </strong>We used EpiTect Methyl II PCR Assays to evaluate DNA methylation of CpG islands located in promoter regions of <i>ENG</i> (CpG Island 114642) and <i>TGFβR2</i> (CpG Island 110111). Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. N = 21 nulliparous preeclampsia case participants were 1:1 frequency matched to N = 21 nulliparous normotensive control participants on gestational age at sample collection (±2 weeks), smoking status, and labor status at sample collection. Methylation values were compared between case and control participant groups [(<i>ENG</i> subset: n = 20 (9 cases, 11 controls); <i>TGFβR2</i> subset: n = 28 (15 cases, 13 controls)].</p><p><strong>Results: </strong>The majority of the preeclampsia cases delivered at ⩾34 weeks' gestation (83%). Average methylation levels for <i>ENG</i> ([M ± (SD)]; Case Participant Group = 6.54% ± 4.57 versus Control Participant group = 4.81% ± 5.08; <i>P</i> = .102) and <i>TGFβR2</i> (Case Participant Group = 1.50% ± 1.37 vs Control Participant Group = 1.70% ± 1.40; <i>P</i> = .695) promoter CpG islands did not differ significantly between the participant groups. Removal of 2 extreme outliers in the <i>ENG</i> analytic subset revealed a trend between levels of <i>ENG</i> methylation and pregnancy outcome (Case Participant Group = 5.17% ± 2.16 vs Control Participant Group = 3.36% ± 1.73; <i>P</i> = .062).</p><p><strong>Conclusion: </strong>Additional epigenetic studies that include larger sample sizes, investigate preeclampsia subtypes, and capture methylation status of CpG island shores and shelves are needed to further inform us of the potential role that <i>ENG</i> and <i>TGFβR2</i> DNA methylation plays in preeclampsia pathophysiology.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720959682"},"PeriodicalIF":2.2,"publicationDate":"2020-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720959682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38527886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}