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Clinical Epigenetics

José García-Solano, María C Turpin, Daniel Torres-Moreno, Francisco Huertas-López, Anne Tuomisto, Markus J Mäkinen, Ana Conesa, Pablo Conesa-Zamora
BACKGROUND: Altered methylation patterns are driving forces in colorectal carcinogenesis. The serrated adenocarcinoma (SAC) and sporadic colorectal carcinoma showing histological and molecular features of microsatellite instability (hmMSI-H) are two endpoints of the so-called serrated pathological route sharing some characteristics but displaying a totally different immune response and clinical outcome. However, there are no studies comparing the methylome of these two subtypes of colorectal carcinomas...
November 9, 2018: Clinical Epigenetics
Riccardo E Marioni, Daniel W Belsky, Ian J Deary, Wolfgang Wagner
Evaluation of biological age, as opposed to chronological age, is of high relevance for interventions to increase healthy ageing. Highly reproducible age-associated DNA methylation (DNAm) changes can be integrated into algorithms for epigenetic age predictions. These predictors have mostly been trained to correlate with chronological age, but they are also indicative for biological ageing. For example, accelerated epigenetic age of blood is associated with higher risk of all-cause mortality in later life. The perceived age of facial images (face-age) is also associated with all-cause mortality and other ageing-associated traits...
November 8, 2018: Clinical Epigenetics
Marisa Claudia Alvarez, Victor Maso, Cristiane Okuda Torello, Karla Priscilla Ferro, Sara Teresinha Olalla Saad
BACKGROUND: In the present study, we investigated the molecular mechanisms underlying the pro-apoptotic effects of quercetin (Qu) by evaluating the effect of Qu treatment on DNA methylation and posttranslational histone modifications of genes related to the apoptosis pathway. This study was performed in vivo in two human xenograft acute myeloid leukemia (AML) models and in vitro using HL60 and U937 cell lines. RESULTS: Qu treatment almost eliminates DNMT1 and DNMT3a expression, and this regulation was in part STAT-3 dependent...
November 8, 2018: Clinical Epigenetics
Sara Daniel, Vibe Nylander, Lars R Ingerslev, Ling Zhong, Odile Fabre, Briana Clifford, Karen Johnston, Richard J Cohn, Romain Barres, David Simar
BACKGROUND: Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory diseases in cancer survivors. RESULTS: To test this hypothesis, we established the epigenetic and transcriptomic profiles of immune cells from 44 childhood cancer survivors (CCS, > 16 years old) on full remission (> 5 years) who had received chemotherapy alone or in combination with total body irradiation (TBI) and hematopoietic stem cell transplant (HSCT)...
November 6, 2018: Clinical Epigenetics
Hongxia Li, Meiying Zhang, Enqiang Linghu, Fuyou Zhou, James G Herman, Liming Hu, Mingzhou Guo
BACKGROUND: The role of TMEM176A in human hepatocellular carcinoma (HCC) is unknown. This study explored the epigenetic regulation and function of TMEM176A in human HCC. MATERIALS AND METHODS: Twelve HCC cell lines and 126 cases of primary cancer were analyzed. Methylation-specific PCR, immunohistochemistry, flow cytometry, and xenograft mouse models were employed. RESULTS: TMEM176A was highly expressed in SNU387, SNU182, Huh1, and SNU475 cells; reduced expression was observed in HepG2 and PLC/PRF/5 cells; and no expression was found in SNU449, HBXF344, SMMC7721, Huh7, and LM3 cells...
November 6, 2018: Clinical Epigenetics
Julius C Pape, Tania Carrillo-Roa, Barbara O Rothbaum, Charles B Nemeroff, Darina Czamara, Anthony S Zannas, Dan Iosifescu, Sanjay J Mathew, Thomas C Neylan, Helen S Mayberg, Boadie W Dunlop, Elisabeth B Binder
BACKGROUND: We have previously evaluated the efficacy of the CRF1 receptor antagonist GSK561679 in female PTSD patients. While GSK561679 was not superior to placebo overall, it was associated with a significantly stronger symptom reduction in a subset of patients with probable CRF system hyperactivity, i.e., patients with child abuse and CRHR1 SNP rs110402 GG carriers. Here, we test whether blood-based DNA methylation levels within CRHR1 and other PTSD-relevant genes would be associated with treatment outcome, either overall or in the high CRF activity subgroup...
November 3, 2018: Clinical Epigenetics
Lien-Hung Huang, Ho-Chang Kuo, Cheng-Tsung Pan, Yeong-Shin Lin, Ying-Hsien Huang, Sung-Chou Li
BACKGROUND: Kawasaki disease (KD) is a prevalent pediatric disease worldwide and can cause coronary artery aneurysm as a severe complication. Typically, DNA methylation is thought to repress the expression of nearby genes. However, the cases in which DNA methylation promotes gene expression have been reported. In addition, globally, to what extent DNA methylation affects gene expression and how it contributes to the pathogenesis of KD are not yet well understood. METHODS: To address these important biological questions, we enrolled subjects, collected DNA and RNA samples from the subjects' total white blood cells, and performed DNA methylation (M450K) and gene expression (HTA 2...
November 1, 2018: Clinical Epigenetics
Fu-Hui Xiao, Xiao-Qiong Chen, Yong-Han He, Qing-Peng Kong
BACKGROUND: Accelerated age-associated DNA methylation changes in males may explain the earlier onset of age-related diseases (e.g., cardiovascular disease (CVD)) and thus contribute to sexually dimorphic morbidity and lifespan. However, the details regarding the emergence of this sex-biased methylation pattern remain unclear. RESULTS: To address these issues, we collected publicly available peripheral blood methylation datasets detected by Illumina HumanMethylation450 BeadChip platform from four studies that contain age and gender information of samples...
October 29, 2018: Clinical Epigenetics
Qiuqin Tang, Feng Pan, Jing Yang, Ziqiang Fu, Yiwen Lu, Xian Wu, Xiumei Han, Minjian Chen, Chuncheng Lu, Yankai Xia, Xinru Wang, Wei Wu
BACKGROUND: Male infertility is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. Abnormal epigenetic programming has been proposed as a possible mechanism compromising male fertility. Recent studies suggest that aberrant imprinting in spermatozoa in a subset of infertile men is a risk factor for congenital diseases in children conceived via assisted reproduction techniques. In this study, we examined the DNA methylation status of CpG sites within the differentially methylated regions (DMRs) of three imprinted genes, H19, GNAS, and DIRAS3, using combined bisulfite PCR restriction analysis and bisulfite sequencing in sperm obtained from 135 men with idiopathic male infertility, including normozoospermia (n = 39), moderate oligozoospermia (n = 45), and severe oligozoospermia (n = 51), and fertile controls (n = 59)...
October 29, 2018: Clinical Epigenetics
Catarina Moreira-Barbosa, Daniela Barros-Silva, Pedro Costa-Pinheiro, Jorge Torres-Ferreira, Vera Constâncio, Rui Freitas, Jorge Oliveira, Luís Antunes, Rui Henrique, Carmen Jerónimo
BACKGROUND: Prostate cancer (PCa) is one of the most common cancers among men worldwide. Current screening methods for PCa display limited sensitivity and specificity, not stratifying for disease aggressiveness. Hence, development and validation of new molecular markers is needed. Aberrant gene promoter methylation is common in PCa and has shown promise as clinical biomarker. Herein, we assessed and compared the diagnostic and prognostic performance of two-gene panel promoter methylation in the same sample sets...
October 29, 2018: Clinical Epigenetics
Raffael Ott, Jens H Stupin, Kerstin Melchior, Karen Schellong, Thomas Ziska, Joachim W Dudenhausen, Wolfgang Henrich, Rebecca C Rancourt, Andreas Plagemann
BACKGROUND: Adiponectin critically contributes to metabolic homeostasis, especially by insulin-sensitizing action. Gestational diabetes mellitus (GDM) is characterized by insulin resistance leading to materno-fetal hyperglycemia and detrimental birth outcomes. By investigating paired subcutaneous (SAT) and visceral adipose tissue (VAT) as well as blood (cell) samples of GDM-affected (n = 25) vs. matched control (n = 30) mother-child dyads of the prospective "EaCH" cohort study, we addressed whether alterations of adiponectin plasma, mRNA, and DNA methylation levels are associated with GDM and offspring characteristics...
October 24, 2018: Clinical Epigenetics
Nikolay Kondratyev, Arkady Golov, Margarita Alfimova, Tatiana Lezheiko, Vera Golimbet
BACKGROUND: Methylation of DNA is associated with a variety of biological processes. With whole-genome studies of DNA methylation, it became possible to determine a set of genomic sites where DNA methylation is associated with a specific phenotype. A method is needed that allows detailed follow-up studies of the sites, including taking into account genetic information. Bisulfite PCR is a natural choice for this kind of task, but multiplexing is one of the most important problems impeding its implementation...
October 23, 2018: Clinical Epigenetics
Per Eystein Lønning, Stian Knappskog
In this letter, we respond to and discuss the recent publication by Al-Moghrabi et al.: Methylation of BRCA1 and MGMT genes in white blood cells are transmitted from mothers to daughters. We discuss their findings with emphasis on two other recently published papers and argue that their data allows no conclusion regarding the transmission of BRCA1 methylation from parent to child.
October 22, 2018: Clinical Epigenetics
Yu Zheng, Baihui Li, Jian Wang, Yanjuan Xiong, Kaiyuan Wang, Ying Qi, Houfang Sun, Lei Wu, Lili Yang
BACKGROUND: SUV39H2 (suppressor of variegation 3-9 homolog 2), which introduces H3K9me3 to induce transcriptional repression, has been reported to play critical roles in heterochromatin maintenance, DNA repair, and recently, carcinogenesis. Dysregulation of SUV39H2 expression has been observed in several types of cancers. However, neither the genomic landscape nor the clinical significance of SUV39H2 in lung adenocarcinoma has been probed comprehensively. METHODS: In this research, we conducted bioinformatics analysis to primarily sort out potential genes with dysregulated expressions...
October 22, 2018: Clinical Epigenetics
Saigopal Somasundaram, Megan E Forrest, Helen Moinova, Allison Cohen, Vinay Varadan, Thomas LaFramboise, Sanford Markowitz, Ahmad M Khalil
BACKGROUND: DNA methylation is a key epigenetic mark in mammalian organisms that plays key roles in chromatin organization and gene expression. Although DNA methylation in gene promoters is generally associated with gene repression, recent studies demonstrate that DNA methylation in gene bodies and intergenic regions of the genome may result in distinct modes of gene regulation. Furthermore, the molecular mechanisms underlying the establishment and maintenance of DNA methylation in human health and disease remain to be fully elucidated...
October 22, 2018: Clinical Epigenetics
Pei-Chien Tsai, Craig A Glastonbury, Melissa N Eliot, Sailalitha Bollepalli, Idil Yet, Juan E Castillo-Fernandez, Elena Carnero-Montoro, Thomas Hardiman, Tiphaine C Martin, Alice Vickers, Massimo Mangino, Kirsten Ward, Kirsi H Pietiläinen, Panos Deloukas, Tim D Spector, Ana Viñuela, Eric B Loucks, Miina Ollikainen, Karl T Kelsey, Kerrin S Small, Jordana T Bell
BACKGROUND: Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear. METHODS: We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins...
October 20, 2018: Clinical Epigenetics
Céline Bruno, Oxana Blagoskonov, Julie Barberet, Magali Guilleman, Sandrine Daniel, Benjamin Tournier, Christine Binquet, Cécile Choux, Patricia Fauque
BACKGROUND: Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neoplasia in situ (GCNIS), present similarities to fetal gonocytes, specifically characterized by global DNA hypomethylation particularly on imprinting sequences. These disorders may have a common origin derived from perturbations of embryonal programming during fetal development...
October 19, 2018: Clinical Epigenetics
Jaya Mary Thomas, Sumi Surendran, Mathew Abraham, Arumugam Rajavelu, Chandrasekharan C Kartha
Upon publication of the original article [1] the authors noticed that the affiliation Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India was missing.
October 17, 2018: Clinical Epigenetics
Lisa M McEwen, Meaghan J Jones, David Tse Shen Lin, Rachel D Edgar, Lucas T Husquin, Julia L MacIsaac, Katia E Ramadori, Alexander M Morin, Christopher F Rider, Chris Carlsten, Lluís Quintana-Murci, Steve Horvath, Michael S Kobor
BACKGROUND: The capacity of technologies measuring DNA methylation (DNAm) is rapidly evolving, as are the options for applicable bioinformatics methods. The most commonly used DNAm microarray, the Illumina Infinium HumanMethylation450 (450K array), has recently been replaced by the Illumina Infinium HumanMethylationEPIC (EPIC array), nearly doubling the number of targeted CpG sites. Given that a subset of 450K CpG sites is absent on the EPIC array and that several tools for both data normalization and analyses were developed on the 450K array, it is important to assess their utility when applied to EPIC array data...
October 16, 2018: Clinical Epigenetics
Alexandra M Binder, Leah T Stiemsma, Kristen Keller, Sanne D van Otterdijk, Verónica Mericq, Ana Pereira, José L Santos, John Shepherd, Karin B Michels
BACKGROUND: Estrogen receptor-α (ER-α) is a transcriptional regulator, which mediates estrogen-dependent breast development, as well as breast tumorigenesis. The influence of epigenetic regulation of ER-α on adolescent breast composition has not been previously studied and could serve as a marker of pubertal health and susceptibility to breast cancer. We investigated the association between ER-α DNA methylation in leukocytes and breast composition in adolescent Chilean girls enrolled in the Growth and Obesity Cohort Study (GOCS) in Santiago, Chile...
October 4, 2018: Clinical Epigenetics
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