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Clinical Epigenetics

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https://read.qxmd.com/read/30777123/a-randomized-controlled-trial-of-folic-acid-intervention-in-pregnancy-highlights-a-putative-methylation-regulated-control-element-at-zfp57
#1
Rachelle E Irwin, Sara-Jayne Thursby, Miroslava Ondičová, Kristina Pentieva, Helene McNulty, Rebecca C Richmond, Aoife Caffrey, Diane J Lees-Murdock, Marian McLaughlin, Tony Cassidy, Matthew Suderman, Caroline L Relton, Colum P Walsh
BACKGROUND: Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86)...
February 18, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30770769/novel-familial-distal-imprinting-centre-1-11p15-5-deletion-provides-further-insights-in-imprinting-regulation
#2
Florian Kraft, Katharina Wesseler, Matthias Begemann, Ingo Kurth, Miriam Elbracht, Thomas Eggermann
BACKGROUND: Deletions of the imprinting centre 1 (IC1) in 11p15.5 are rare and their clinical significance is not only influenced by their parental origin but also by their exact genomic localization. In case the maternal IC1 allele is affected, the deletion is associated with the overgrowth disorder Beckwith-Wiedemann syndrome (BWS) and a gain of methylation (GOM) of the IC1. The consequences of deletions of the paternal IC1 allele depend on the localization and probably the binding sites of methylation-specific DNA-binding factors affected by the change...
February 15, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30764859/targeted-design-and-identification-of-ac1nod4q-to-block-activity-of-hotair-by-abrogating-the-scaffold-interaction-with-ezh2
#3
Yu Ren, Yun-Fei Wang, Jing Zhang, Qi-Xue Wang, Lei Han, Mei Mei, Chun-Sheng Kang
BACKGROUND: Nearly 25% of long intergenic non-coding RNAs (lincRNAs) recruit chromatin-modifying proteins (e.g., EZH2) to silence target genes. HOX antisense intergenic RNA (HOTAIR) is deregulated in diverse cancers and could be an independent and powerful predictor of eventual metastasis and death. Yet, it is challenging to develop small molecule drugs to block activity of HOTAIR with high specificity in a short time. RESULTS: Our previous study proved that the 5' domain, but not its 3' domain, was the function domain of HOTAIR responsible for tumorigenesis and metastasis in glioblastoma and breast cancer, by recruiting and binding EZH2...
February 14, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30760335/association-of-recurrent-venous-thromboembolism-and-circulating-micrornas
#4
Xiao Wang, Kristina Sundquist, Peter J Svensson, Hamideh Rastkhani, Karolina Palmér, Ashfaque A Memon, Jan Sundquist, Bengt Zöller
BACKGROUND: Patients with unprovoked first venous thromboembolism (VTE) are at a high risk of recurrence. Although circulating microRNAs (miRNAs) have been found to be associated with VTE and are markers of hypercoagulability, this study is the first to examine whether circulating miRNAs are associated with the risk of VTE recurrence. RESULTS: A nested case-control study design was used where plasma samples were obtained from 78 patients with unprovoked VTE from the Malmö Thrombophilia Study (MATS)...
February 13, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30760334/epigenetic-findings-in-periodontitis-in-uk-twins-a-cross-sectional-study
#5
Yuko Kurushima, Pei-Chien Tsai, Juan Castillo-Fernandez, Alexessander Couto Alves, Julia Sarah El-Sayed Moustafa, Caroline Le Roy, Tim D Spector, Mark Ide, Francis J Hughes, Kerrin S Small, Claire J Steves, Jordana T Bell
BACKGROUND: Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease. METHODS: Self-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease...
February 13, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30744689/the-role-and-mechanisms-of-action-of-micrornas-in-cancer-drug-resistance
#6
REVIEW
Wengong Si, Jiaying Shen, Huilin Zheng, Weimin Fan
MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19-25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified drug targets, altered cell cycle checkpoints, or increased DNA damage repair, among others...
February 11, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30744680/analysis-of-two-birth-tissues-provides-new-insights-into-the-epigenetic-landscape-of-neonates-born-preterm
#7
Yonghui Wu, Xinyi Lin, Ives Yubin Lim, Li Chen, Ai Ling Teh, Julia L MacIsaac, Kok Hian Tan, Michael S Kobor, Yap Seng Chong, Peter D Gluckman, Neerja Karnani
BACKGROUND: Preterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfortunately, our understanding of the molecular pathways associated with PTB remains limited. There is a growing body of evidence suggesting the role of DNA methylation (DNAm) in mediating the effects of PTB on future health outcomes...
February 11, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30744671/identification-of-potential-blood-biomarkers-for-parkinson-s-disease-by-gene-expression-and-dna-methylation-data-integration-analysis
#8
Changliang Wang, Liang Chen, Yang Yang, Menglei Zhang, Garry Wong
BACKGROUND: Blood-based gene expression or epigenetic biomarkers of Parkinson's disease (PD) are highly desirable. However, accuracy and specificity need to be improved, and methods for the integration of gene expression with epigenetic data need to be developed in order to make this feasible. METHODS: Whole blood gene expression data and DNA methylation data were downloaded from Gene Expression Omnibus (GEO) database. A linear model was used to identify significantly differentially expressed genes (DEGs) and differentially methylated genes (DMGs) according to specific gene regions 5'-C-phosphate-G-3' (CpGs) or all gene regions CpGs in PD...
February 11, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30736859/dna-methylome-profiling-of-all-cause-mortality-in-comparison-with-age-associated-methylation-patterns
#9
Jesper Beltoft Lund, Shuxia Li, Jan Baumbach, Anne Marie Svane, Jacob Hjelmborg, Lene Christiansen, Kaare Christensen, Paul Redmond, Riccardo E Marioni, Ian J Deary, Qihua Tan
BACKGROUND: Multiple epigenome-wide association studies have been performed to identify DNA methylation patterns regulated by aging or correlated with risk of death. However, the inter-relatedness of the epigenetic basis of aging and mortality has not been well investigated. METHODS: Using genome-wide DNA methylation data from the Lothian Birth Cohorts, we conducted a genome-wide association analysis of all-cause mortality and compared this with age-associated methylation patterns reported on the same samples...
February 8, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30736847/hsa_circrna_0054633-is-highly-expressed-in-gestational-diabetes-mellitus-and-closely-related-to-glycosylation-index
#10
Hangyu Wu, Siyang Wu, Yingchao Zhu, Mei Ye, Jun Shen, Yan Liu, Yisheng Zhang, Shizhong Bu
BACKGROUND: Circular RNA (circRNA) is involved in the pathological processes of various diseases. CircRNA is more stable than linear RNAs and is expressed in high levels in tissues, making it a better biomarker candidate than linear RNAs. In this study, we aimed to identify potential circRNA biomarkers of gestational diabetes mellitus (GDM). METHODS: A retrospective case-control study was conducted using data and samples from women treated at a hospital in China between July 10, 2017, and February 15, 2018...
February 8, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30732658/association-of-four-imprinting-disorders-and-art
#11
Hiromitsu Hattori, Hitoshi Hiura, Akane Kitamura, Naoko Miyauchi, Norio Kobayashi, Souta Takahashi, Hiroaki Okae, Koichi Kyono, Masayo Kagami, Tsutomu Ogata, Takahiro Arima
BACKGROUND: Human-assisted reproductive technologies (ART) are a widely accepted treatment for infertile couples. At the same time, many studies have suggested the correlation between ART and increased incidences of normally rare imprinting disorders such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Silver-Russell syndrome (SRS). Major methylation dynamics take place during cell development and the preimplantation stages of embryonic development...
February 7, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30732639/maternal-obesity-influences-expression-and-dna-methylation-of-the-adiponectin-and-leptin-systems-in-human-third-trimester-placenta
#12
Perrine Nogues, Esther Dos Santos, Hélène Jammes, Paul Berveiller, Lucie Arnould, François Vialard, Marie-Noëlle Dieudonné
BACKGROUND: It is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin. Furthermore, it was recently reported that maternal obesity has a significant impact on placental development. Leptin and adiponectin are present at the fetal-maternal interface and are involved in the development of a functional placenta. However, less is known about leptin and adiponectin's involvement in the placental alterations described in obese women...
February 7, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30717815/exploring-the-effect-of-antenatal-depression-treatment-on-children-s-epigenetic-profiles-findings-from-a-pilot-randomized-controlled-trial
#13
Laura S Bleker, Jeannette Milgrom, Alexandra Sexton-Oates, Tessa J Roseboom, Alan W Gemmill, Christopher J Holt, Richard Saffery, Huibert Burger, Susanne R de Rooij
BACKGROUND: Children prenatally exposed to maternal depression more often show behavioral and emotional problems compared to unexposed children, possibly through epigenetic alterations. Current evidence is largely based on animal and observational human studies. Therefore, evidence from experimental human studies is needed. In this follow-up of a small randomized controlled trial (RCT), DNA-methylation was compared between children of women who had received cognitive behavioral therapy (CBT) for antenatal depression and children of women who had received treatment as usual (TAU)...
February 4, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30717806/tracking-of-epigenetic-changes-during-hematopoietic-differentiation-of-induced-pluripotent-stem-cells
#14
Olivia Cypris, Joana Frobel, Shivam Rai, Julia Franzen, Stephanie Sontag, Roman Goetzke, Marcelo A Szymanski de Toledo, Martin Zenke, Wolfgang Wagner
BACKGROUND: Differentiation of induced pluripotent stem cells (iPSCs) toward hematopoietic progenitor cells (HPCs) raises high hopes for disease modeling, drug screening, and cellular therapy. Various differentiation protocols have been established to generate iPSC-derived HPCs (iHPCs) that resemble their primary counterparts in morphology and immunophenotype, whereas a systematic epigenetic comparison was yet elusive. RESULTS: In this study, we compared genome-wide DNA methylation (DNAm) patterns of iHPCs with various different hematopoietic subsets...
February 4, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30709423/trim4-is-associated-with-neural-tube-defects-based-on-genome-wide-dna-methylation-analysis
#15
Henan Zhang, Yi Guo, Hui Gu, Xiaowei Wei, Wei Ma, Dan Liu, Kun Yu, Wenting Luo, Ling Ma, Yusi Liu, Jia Xue, Jieting Huang, Yanfu Wang, Shanshan Jia, Naixuan Dong, Hongyan Wang, Zhengwei Yuan
BACKGROUND: Neural tube defects (NTDs) are complex abnormalities associated with gene-environment interactions. The underlying cause has not been determined. METHODS: Spinal cord tissues from cases with NTDs and healthy controls were collected. Methylation patterns between cases and normal individuals were compared using 450K Infinium Methylation BeadChip Illumina. DNA methylation analysis by pyrosequencing (PyroMark Q96) and mRNA and protein expression were analyzed using real-time quantitative PCR and Western blotting, respectively...
February 1, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30700309/epigenetic-biomarker-screening-by-flim-fret-for-combination-therapy-in-er-breast-cancer
#16
Wenjie Liu, Yi Cui, Wen Ren, Joseph Irudayaraj
Hormone-dependent gene expression involves dynamic and orchestrated regulation of epigenome leading to a cancerous state. Estrogen receptor (ER)-positive breast cancer rely on chromatin remodeling and association with epigenetic factors in inducing ER-dependent oncogenesis and thus cell over-proliferation. The mechanistic differences between epigenetic regulation and hormone signaling provide an avenue for combination therapy of ER-positive breast cancer. We hypothesized that epigenetic biomarkers within single nucleosome proximity of ER-dependent genes could serve as potential therapeutic targets...
January 30, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30678737/improved-filtering-of-dna-methylation-microarray-data-by-detection-p-values-and-its-impact-on-downstream-analyses
#17
Jonathan A Heiss, Allan C Just
BACKGROUND: DNA methylation microarrays are popular for epigenome-wide association studies (EWAS), but spurious values complicate downstream analysis and threaten replication. Conventional cut-offs for detection p values for filtering out undetected probes were demonstrated in a single previous study as insufficient leading to many apparent methylation calls in samples from females in probes targeting the Y-chromosome. We present an alternative approach to calculate more accurate detection p values utilizing non-specific background fluorescence...
January 24, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30678711/the-associations-of-dna-methylation-alterations-in-oxidative-stress-related-genes-with-cancer-incidence-and-mortality-outcomes-a-population-based-cohort-study
#18
Xīn Gào, Yan Zhang, Barbara Burwinkel, Yang Xuan, Bernd Holleczek, Hermann Brenner, Ben Schöttker
BACKGROUND: Reactive oxygen species may be involved in epigenetic gene activation or silencing. We aimed to identify CpG sites, at which DNA methylation is related to urinary 8-isoprostane levels (biomarker of lipid peroxidation) and cancer or mortality outcomes. This investigation was based on a German, population-based cohort with linkage to cancer and mortality registry data (2000-2016). RESULTS: Blood DNA methylation in promoter regions of 519 genes, known to be involved in pathways from oxidative stress (OS) to cancer, was obtained at the cohort's baseline examination...
January 24, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30665459/aberrant-methylation-of-pax3-gene-and-neural-tube-defects-in-association-with-exposure-to-polycyclic-aromatic-hydrocarbons
#19
Shanshan Lin, Aiguo Ren, Linlin Wang, Chloe Santos, Yun Huang, Lei Jin, Zhiwen Li, Nicholas D E Greene
BACKGROUND: Neural tube defects (NTDs) are common and severe congenital malformations. Pax3 is an essential gene for neural tube closure in mice but it is unknown whether altered expression or methylation of PAX3 contributes to human NTDs. We examined the potential role of hypermethylation of Pax3 in the development of NTDs by analyzing human NTD cases and a mouse model in which NTDs were induced by benzo[a]pyrene (BaP), a widely studied polycyclic aromatic hydrocarbon (PAH). METHODS: We extracted methylation information of PAX3 in neural tissues from array data of ten NTD cases and eight non-malformed controls...
January 21, 2019: Clinical Epigenetics
https://read.qxmd.com/read/30660189/leisure-time-physical-activity-and-dna-methylation-age-a-twin-study
#20
Elina Sillanpää, Miina Ollikainen, Jaakko Kaprio, Xiaoling Wang, Tuija Leskinen, Urho M Kujala, Timo Törmäkangas
BACKGROUND: Epigenetic clocks may increase our understanding on human aging and how genetic and environmental factors regulate an individual aging process. One of the most promising clocks is Horvath's DNA methylation (DNAm) age. Age acceleration, i.e., discrepancy between DNAm age and chronological age, tells us whether the person is biologically young or old compared to his/her chronological age. Several environmental and lifestyle factors have been shown to affect life span. We investigated genetic and environmental predictors of DNAm age in young and older monozygotic (MZ) and dizygotic (DZ) twins with a focus on leisure time physical activity...
January 19, 2019: Clinical Epigenetics
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