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Stephanie Shiau, Renate Strehlau, Jing Shen, Avy Violari, Faeezah Patel, Afaaf Liberty, Marc Foca, Shuang Wang, Mary Beth Terry, Michael T Yin, Ashraf Coovadia, Elaine J Abrams, Stephen M Arpadi, Louise Kuhn
BACKGROUND: Data on accelerated aging in HIV-infected children are limited. In this study we assess two biomarkers of aging - telomere length and DNA methylation (DNAm) age - in a cohort of early-treated HIV-infected children and compare these aging biomarkers to HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children. SETTING: Cross-sectional study of 120 HIV-infected, 33 HEU, and 25 HUU children enrolled in a cohort study in Johannesburg, South Africa...
April 27, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Walter J Jessen, Michael F Borgerding, G L Prasad
PURPOSE: Alternations in gene methylation and other epigenetic changes regulate normal development as well as drive disease progression. The aim of this study is to investigate global methylation changes in the buccal cells of smokers and smokeless tobacco users. MATERIALS AND METHODS: Generally healthy adult male subjects were recruited into Smoker (SMK), Moist Snuff Consumer (MSC) and Non-Tobacco Consumer (NTC) cohorts (40 subjects/cohort) ( Identifier: NCT01923402)...
May 17, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Andrew D Beggs, Jonathan James, Germaine Caldwell, Toby Prout, Mark P Dilworth, Phillipe Taniere, Tariq Iqbal, Dion G Morton, Glenn Matthews
Background and aims: Ulcerative colitis (UC) is associated with a higher background risk of dysplasia and/or neoplasia due to chronic inflammation. There exist few biomarkers for identification of patients with dysplasia, and targeted biopsies in this group of patients are inaccurate in reliably identifying dysplasia. We aimed to examine the epigenome of UC dysplasia and to identify and validate potential biomarkers. Methods: Colonic samples from patients with UC-associated dysplasia or neoplasia underwent epigenome-wide analysis on the Illumina 450K methylation array...
May 14, 2018: Inflammatory Bowel Diseases
Emma E Thompson, Jessie Nicodemus-Johnson, Kyung Won Kim, James E Gern, Daniel J Jackson, Robert F Lemanske, Carole Ober
Background: The changes that occur during puberty have been implicated in susceptibility to a wide range of diseases later in life, many of which are characterized by sex-specific differences in prevalence. Both genetic and environmental factors have been associated with the onset or delay of puberty, and recent evidence has suggested a role for epigenetic changes in the initiation of puberty as well. Objective: To identify global DNA methylation changes that arise across the window of puberty in girls and boys...
2018: Clinical Epigenetics
Chunxiao Li, Wenjing Gao, Ying Gao, Canqing Yu, Jun Lv, Ruoran Lv, Jiali Duan, Ying Sun, Xianghui Guo, Weihua Cao, Liming Li
The DNA methylation age, a good reflection of human aging process, has been used to predict chronological age of adults and newborns. However, the prediction model for children and adolescents was absent. In this study, we aimed to generate a prediction model of chronological age for children and adolescents aged 6-17 years by using age-specific DNA methylation patterns from 180 Chinese twin individuals. We identified 6,350 age-related CpGs from the epigenome-wide association analysis (N=179). 116 known age-related sites in children were confirmed...
May 12, 2018: Aging
Emmanuel Karouzakis, Karim Raza, Christoph Kolling, Christopher D Buckley, Steffen Gay, Andrew Filer, Caroline Ospelt
DNA methylation is an important epigenetic modification that is known to be altered in rheumatoid arthritis synovial fibroblasts (RASF). Here, we compared the status of promoter DNA methylation of SF from patients with very early RA with SF from patients with resolving arthritis, fully established RA and from non-arthritic patients. DNA was hybridized to Infinium Human methylation 450k and 850k arrays and differential methylated genes and pathways were identified. We could identify a significant number of CpG sites that differed between the SF of different disease stages, showing that epigenetic changes in SF occur early in RA development...
May 9, 2018: Scientific Reports
Ana B Crujeiras, Sonsoles Morcillo, Angel Diaz-Lagares, Juan Sandoval, Daniel Castellano-Castillo, Esperanza Torres, David Hervas, Sebastian Moran, Manel Esteller, Manuel Macias-Gonzalez, Felipe F Casanueva, Francisco J Tinahones
BACKGROUND: Obesity was established as a relevant modifiable risk factor in the onset and progression of colorectal cancer (CRC). This relationship could be mediated by an epigenetic regulation. OBJECTIVES: The current work aimed to explore the effects of excess body weight on the DNA methylation profile of CRC using a genome-wide DNA methylation approach and to identify an epigenetic signature of obesity-related CRC. METHODS: Fifty-six CRC-diagnosed patients (50 years) were included in the study and categorized according to their body mass index (BMI) as non-obese (BMI ≤ 25 kg/m2 ) or overweight/obese (BMI > 25 kg/m2 )...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Leonidas Chouliaras, Ehsan Pishva, Rita Haapakoski, Eniko Zsoldos, Abda Mahmood, Nicola Filippini, Joe Burrage, Jonathan Mill, Mika Kivimäki, Katie Lunnon, Klaus P Ebmeier
AIM: The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. METHODS: We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. RESULTS: Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy...
April 25, 2018: Epigenomics
Sabine A S Langie, Matthieu Moisse, Katarzyna Szarc Vel Szic, Ellen Van Der Plas, Gudrun Koppen, Sofie De Prins, Tijs Louwies, Vera Nelen, Guy Van Camp, Diether Lambrechts, Greet Schoeters, Wim Vanden Berghe, Patrick De Boever
Background: The prevalence of respiratory allergy in children is increasing. Epigenetic DNA methylation changes are plausible underlying molecular mechanisms. Results: Saliva samples collected in substudies of two longitudinal birth cohorts in Belgium (FLEHS1 & FLEHS2) were used to discover and confirm DNA methylation signatures that can differentiate individuals with respiratory allergy from healthy subjects. Genome-wide analysis with Illumina Methylation 450K BeadChips revealed 23 differentially methylated gene regions (DMRs) in saliva from 11y old allergic children (N=26) vs...
2018: Clinical Epigenetics
Zhenxing Wang, XiaoLiang Wu, Yadong Wang
BACKGROUND: DNA methylation has been identified to be widely associated to complex diseases. Among biological platforms to profile DNA methylation in human, the Illumina Infinium HumanMethylation450 BeadChip (450K) has been accepted as one of the most efficient technologies. However, challenges exist in analysis of DNA methylation data generated by this technology due to widespread biases. RESULTS: Here we proposed a generalized framework for evaluating data analysis methods for Illumina 450K array...
April 11, 2018: BMC Bioinformatics
H-G Wirsching, G Tabatabai, U Roelcke, A F Hottinger, F Jörger, A Schmid, L Plasswilm, D Schrimpf, C Mancao, D Capper, K Conen, T Hundsberger, F Caparrotti, R von Moos, C Riklin, J Felsberg, P Roth, D T W Jones, S Pfister, E J Rushing, L Abrey, G Reifenberger, L Held, A von Deimling, A Ochsenbein, M Weller
Background: The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT→TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population. Patients and Methods: ARTE was a 2:1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg x 14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years...
April 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Li Chen, Yanbin Dong, Xiaoling Wang, Guang Hao, Ying Huang, Bernard Gutin, Haidong Zhu
SCOPE: Low fiber intake is associated with increased risk for cardiovascular disease (CVD) and cancer. However, the underlying mechanisms are not well understood. We tested two hypotheses: 1) dietary fiber would be associated with DNA methylation levels; 2) those DNA methylation changes would be associated with visceral adiposity and inflammation. We also explored the possibility that the associations between fiber and DNA methylation levels might be confounded with folic acid intake as sensitivity analysis...
April 12, 2018: Molecular Nutrition & Food Research
Kunio Miyake, Akio Kawaguchi, Ryu Miura, Sachiko Kobayashi, Nguyen Quoc Vuong Tran, Sumitaka Kobayashi, Chihiro Miyashita, Atsuko Araki, Takeo Kubota, Zentaro Yamagata, Reiko Kishi
Maternal smoking is reported to cause adverse effects on the health of the unborn child, the underlying mechanism for which is thought to involve alterations in DNA methylation. We examined the effects of maternal smoking on DNA methylation in cord blood, in 247 mother-infant pairs in the Sapporo cohort of the Hokkaido Study, using the Infinium HumanMethylation 450K BeadChip. We first identified differentially methylated CpG sites with a false discovery rate (FDR) of <0.05 and the magnitude of DNA methylation changes (|β| >0...
April 4, 2018: Scientific Reports
E M Price, Wendy P Robinson
It is well-known, but frequently overlooked, that low- and high-throughput molecular data may contain batch effects, i.e., systematic technical variation. Confounding of experimental batches with the variable(s) of interest is especially concerning, as a batch effect may then be interpreted as a biologically significant finding. An integral step toward reducing false discovery in molecular data analysis includes inspection for batch effects and accounting for this signal if present. In a 30-sample pilot Illumina Infinium HumanMethylation450 (450k array) experiment, we identified two sources of batch effects: row and chip...
2018: Frontiers in Genetics
Juozas Gordevičius, Algimantas Kriščiūnas, Daniel E Groot, Steven M Yip, Miki Susic, Andrew Kwan, Rafal Kustra, Anthony M Joshua, Kim N Chi, Art Petronis, Gabriel Oh
PURPOSE: Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20-40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance. EXPERIMENTAL DESIGN: We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients...
April 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
S Cante, S J Beecher, J I Mackenzie
The Energy Transfer Upconversion (ETU) macroparameter is measured for Nd-doped GdVO4 and YVO4 samples at temperatures ranging from Room Temperature (RT) to 450K, by means of a simple and automated z-scan technique. Furthermore, the ground state absorption cross section into the2 H9/2 +4 F5/2 energy levels is characterised for both crystals over the same range of temperatures. The 808 nm π-polarisation absorption cross section is found to decrease from (58.6 ± 0.2) pm2 to (30.9 ± 0.6) pm2 for Nd:YVO4 and (54...
March 19, 2018: Optics Express
Izaskun Mallona, Alberto Sierco, Miguel A Peinado
The Cancer Genome Atlas (TCGA) epigenome data includes the DNA methylation status of tumor and normal tissues of large cohorts for dozens of cancer types. Due to the moderately large data sizes, retrieving and analyzing them requires basic programming skills. Simple data browsing (e.g., candidate gene search) is hampered by the scarcity of easy-to-use data browsers addressed to the broad community of biomedical researchers. We propose a new visualization method depicting the overall DNA methylation status at each TCGA cohort while emphasizing its heterogeneity, thus facilitating the evaluation of the cohort variability and the normal versus tumor differences...
2018: Methods in Molecular Biology
Peter Henneman, Arjan Bouman, Adri Mul, Lia Knegt, Anne-Marie van der Kevie-Kersemaekers, Nitash Zwaveling-Soonawala, Hanne E J Meijers-Heijboer, A S Paul van Trotsenburg, Marcel M Mannens
INTRODUCTION: Down syndrome (DS) is the most frequent genetic cause of intellectual disability. Despite the fact that more than 50 years have passed since the discovery of its genetic aberrations, the exact pathogenesis of the DS phenotype has remained largely unexplained. It was recently hypothesized that the DS pathogenesis involves complex (epi)genetic, molecular and cellular determinants. To date, many reports have addressed epigenetic aberrations associated with DS at different developmental stages/ages and tissue types, but to our best knowledge not in DS newborns...
2018: PloS One
Xiaoling Weng, Fatao Liu, Hong Zhang, Mengyuan Kan, Ting Wang, Mingyue Dong, Yun Liu
BACKGROUND: Offspring exposed to gestational diabetes mellitus (GDM) are at a high risk for metabolic diseases. The mechanisms behind the association between offspring exposed to GDM in utero and an increased risk of health consequences later in life remain unclear. The aim of this study was to clarify the changes in methylation levels in the foetuses of women with GDM and to explore the possible mechanisms linking maternal GDM with a high risk of metabolic diseases in offspring later in life...
March 26, 2018: Diabetes Research and Clinical Practice
Y Alkhaled, M Laqqan, S Tierling, C Lo Porto, M E Hammadeh
The epigenetic mechanism plays an important role in spermatogenesis such as DNA methylation where this episode is represented by either switching genes on or off. Twenty-eight samples (14 case and 14 controls) were subjected to Infinium 450K BeadChip arrays to identify genomic regions that differ in sperm DNA methylation patterns in the subfertile compared to the proven fertile group. Then two CpGs were validated by deep bisulphite sequencing on 82 sperm samples. The results screening study revealed eight CpGs were significantly different in their sperm DNA methylation levels between cases and control group...
March 25, 2018: Andrologia
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