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Clinical Epigenetics

Qingsheng Kong, Yongnan Hao, Xin Li, Xin Wang, Bingyuan Ji, Yili Wu
Stroke is one of the leading causes of death and disability worldwide, and the majority of the cases are ischemic stroke. However, it still lacks effective treatment except for thrombolytic therapy in an extremely narrow time window. Increased evidence suggests that histone deacetylase 4 (HDAC4) was dysregulated in ischemic stroke, which plays a key role in the pathogenesis of ischemic stroke and post-stroke recovery by affecting neuronal death, angiogenesis, and neurogenesis. Therefore, we aim to review the dysregulation of HDAC4 in ischemic stroke and the role of dysregulated HDAC4 in the pathogenesis of ischemic stroke...
September 12, 2018: Clinical Epigenetics
Idoia Blanco-Luquin, Miren Altuna, Javier Sánchez-Ruiz de Gordoa, Amaya Urdánoz-Casado, Miren Roldán, María Cámara, Victoria Zelaya, María Elena Erro, Carmen Echavarri, Maite Mendioroz
BACKGROUND: Whole-exome sequencing has revealed a rare missense variant in PLD3 gene (rs145999145) to be associated with late onset Alzheimer's disease (AD). Nevertheless, the association remains controversial and little is known about the role of PLD3 in AD. Interestingly, PLD3 encodes a phospholipase that may be involved in amyloid precursor protein (APP) processing. Our aim was to gain insight into the epigenetic mechanisms regulating PLD3 gene expression in the human hippocampus affected by AD...
September 12, 2018: Clinical Epigenetics
Min Wang, Weimin Kong, Biyu He, Zhongqi Li, Huan Song, Peiyi Shi, Jianming Wang
BACKGROUND: A variety of abnormalities in vitamin D metabolism have been reported in patients with active tuberculosis. However, intervention trials have produced inconsistent results. We hypothesized that genetic and epigenetic changes in the key genes of the vitamin D metabolic pathway may partly explain the differences between studies. METHODS: We performed a case-control study followed by a prospective cohort study. We recruited 122 patients with pulmonary tuberculosis and 118 healthy controls...
September 12, 2018: Clinical Epigenetics
Yishui Lian, Lingjiao Meng, Pingan Ding, Meixiang Sang
The melanoma antigen gene (MAGE) proteins are a group of highly conserved family members that contain a common MAGE homology domain. Type I MAGEs are relevant cancer-testis antigens (CTAs), and originally considered as attractive targets for cancer immunotherapy due to their typically high expression in tumor tissues but restricted expression in normal adult tissues. Here, we reviewed the recent discoveries and ideas that illustrate the biological functions of MAGE family in cancer progression. Furthermore, we also highlighted the current understanding of the epigenetic mechanism of MAGE family expression in human cancers...
September 5, 2018: Clinical Epigenetics
Vinod Dagar, Wendy Hutchison, Andrea Muscat, Anita Krishnan, David Hoke, Ashley Buckle, Priscillia Siswara, David J Amor, Jeffrey Mann, Jason Pinner, Alison Colley, Meredith Wilson, Rani Sachdev, George McGillivray, Matthew Edwards, Edwin Kirk, Felicity Collins, Kristi Jones, Juliet Taylor, Ian Hayes, Elizabeth Thompson, Christopher Barnett, Eric Haan, Mary-Louise Freckmann, Anne Turner, Susan White, Ben Kamien, Alan Ma, Fiona Mackenzie, Gareth Baynam, Cathy Kiraly-Borri, Michael Field, Tracey Dudding-Byth, Elizabeth M Algar
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder with a population frequency of approximately 1 in 10,000. The most common epigenetic defect in BWS is a loss of methylation (LOM) at the 11p15.5 imprinting centre, KCNQ1OT1 TSS-DMR, and affects 50% of cases. We hypothesised that genetic factors linked to folate metabolism may play a role in BWS predisposition via effects on methylation maintenance at KCNQ1OT1 TSS-DMR. RESULTS: Single nucleotide variants (SNVs) in the folate pathway affecting methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR), cystathionine beta-synthase (CBS) and methionine adenosyltransferase (MAT1A) were examined in 55 BWS patients with KCNQ1OT1 TSS-DMR LOM and in 100 unaffected cases...
August 30, 2018: Clinical Epigenetics
Erin W Hofstatter, Steve Horvath, Disha Dalela, Piyush Gupta, Anees B Chagpar, Vikram B Wali, Veerle Bossuyt, Anna Maria Storniolo, Christos Hatzis, Gauri Patwardhan, Marie-Kristin Von Wahlde, Meghan Butler, Lianne Epstein, Karen Stavris, Tracy Sturrock, Alexander Au, Stephanie Kwei, Lajos Pusztai
BACKGROUND: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. RESULTS: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples)...
August 29, 2018: Clinical Epigenetics
Zhen He, Rong Zhang, Feng Jiang, Hong Zhang, Aihua Zhao, Bo Xu, Li Jin, Tao Wang, Wei Jia, Weiping Jia, Cheng Hu
BACKGROUND: Genome-wide association studies (GWASs) have shown that genetic variants are important determinants of free fatty acid levels. The mechanisms underlying the associations between genetic variants and free fatty acid levels are incompletely understood. Here, we aimed to identify genetic markers that could influence diverse fatty acid levels in a Chinese population and uncover the molecular mechanisms in terms of DNA methylation and gene expression. RESULTS: We identified strong associations between single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) region and multiple polyunsaturated fatty acids...
August 29, 2018: Clinical Epigenetics
Sungshim L Park, Yesha M Patel, Lenora W M Loo, Daniel J Mullen, Ite A Offringa, Alika Maunakea, Daniel O Stram, Kimberly Siegmund, Sharon E Murphy, Maarit Tiirikainen, Loïc Le Marchand
BACKGROUND: Lung cancer is the leading cause of cancer-related death. While cigarette smoking is the primary cause of this malignancy, risk differs across racial/ethnic groups. For the same number of cigarettes smoked, Native Hawaiians compared to whites are at greater risk and Japanese Americans are at lower risk of developing lung cancer. DNA methylation of specific CpG sites (e.g., in AHRR and F2RL3) is the most common blood epigenetic modification associated with smoking status. However, the influence of internal smoking dose, measured by urinary nicotine equivalents (NE), on DNA methylation in current smokers has not been investigated, nor has a study evaluated whether for the same smoking dose, circulating leukocyte DNA methylation patterns differ by race...
August 23, 2018: Clinical Epigenetics
Daniela Nasif, Emanuel Campoy, Sergio Laurito, Richard Branham, Guillermo Urrutia, María Roqué, María T Branham
BACKGROUND: Inhibitor of differentiation protein 4 (ID4) is a dominant negative regulator of the basic helix-loop-helix (bHLH) family of transcription factors. During tumorigenesis, ID4 may act as a tumor suppressor or as an oncogene in different tumor types. However, the role of ID4 in breast cancer is not clear where both an oncogenic and a tumor suppressor function have been attributed. Here, we hypothesize that ID4 behaves as both, but its role in breast differs according to the estrogen receptor (ER) status of the tumor...
August 23, 2018: Clinical Epigenetics
Mara Thomas, Nora Knoblich, Annalena Wallisch, Katarzyna Glowacz, Julia Becker-Sadzio, Friederike Gundel, Christof Brückmann, Vanessa Nieratschker
BACKGROUND: The importance of epigenetic alterations in psychiatric disorders is increasingly acknowledged and the use of DNA methylation patterns as markers of disease is a topic of ongoing investigation. Recent studies suggest that patients suffering from Borderline Personality Disorder (BPD) display differential DNA methylation of various genes relevant for neuropsychiatric conditions. For example, several studies report differential methylation in the promoter region of the brain-derived neurotrophic factor gene (BDNF) in blood...
August 22, 2018: Clinical Epigenetics
Aditi Chandra, Swapan Senapati, Sudipta Roy, Gobinda Chatterjee, Raghunath Chatterjee
BACKGROUND: Psoriasis is a chronic inflammatory autoimmune skin disorder. Several studies suggested psoriasis to be a complex multifactorial disease, but the exact triggering factor is yet to be determined. Evidences suggest that in addition to genetic factors, epigenetic reprogramming is also involved in psoriasis development. Major histopathological features, like increased proliferation and abnormal differentiation of keratinocytes, and immune cell infiltrations are characteristic marks of psoriatic skin lesions...
August 9, 2018: Clinical Epigenetics
Kuang-Tai Kuo, Wen-Chien Huang, Oluwaseun Adebayo Bamodu, Wei-Hwa Lee, Chun-Hua Wang, M Hsiao, Liang-Shun Wang, Chi-Tai Yeh
BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. METHODS: We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines...
August 9, 2018: Clinical Epigenetics
Rubén Rodríguez Bautista, Alette Ortega Gómez, Alfredo Hidalgo Miranda, Alejandro Zentella Dehesa, Cynthia Villarreal-Garza, Federico Ávila-Moreno, Oscar Arrieta
Upon publication of the original article [1], the authors noticed that the Figs. 1, 2 and 3 were incorrectly given.
August 8, 2018: Clinical Epigenetics
Tine Maj Storebjerg, Siri H Strand, Søren Høyer, Anne-Sofie Lynnerup, Michael Borre, Torben F Ørntoft, Karina D Sørensen
BACKGROUND: Prognostic tools for prostate cancer (PC) are inadequate and new molecular biomarkers may improve risk stratification. The epigenetic mark 5-hydroxymethylcytosine (5hmC) has recently been proposed as a novel candidate prognostic biomarker in several malignancies including PC. 5hmC is an oxidized derivative of 5-methylcytosine (5mC) and can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The present study is the first to investigate the biomarker potential in PC for all four DNA methylation marks in parallel...
August 7, 2018: Clinical Epigenetics
Varun Sasidharan Nair, Salman M Toor, Rowaida Z Taha, Hibah Shaath, Eyad Elkord
BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed human malignancy worldwide. Upregulation of inhibitory immune checkpoints by tumor-infiltrating immune cells (TIICs) or their ligands by tumor cells leads to tumor evasion from host immunosurveillance. Changes in DNA methylation pattern and enrichment of methylated histone marks in the promoter regions could be major contributors to the upregulation of immune checkpoints (ICs) in the tumor microenvironment (TME)...
August 6, 2018: Clinical Epigenetics
Emma Ahlén Bergman, Ciputra Adijaya Hartana, Markus Johansson, Ludvig B Linton, Sofia Berglund, Martin Hyllienmark, Christian Lundgren, Benny Holmström, Karin Palmqvist, Johan Hansson, Farhood Alamdari, Ylva Huge, Firas Aljabery, Katrine Riklund, Malin E Winerdal, David Krantz, A Ali Zirakzadeh, Per Marits, Louise K Sjöholm, Amir Sherif, Ola Winqvist
BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies...
August 3, 2018: Clinical Epigenetics
Jiangxia Fan, Yan Zhang, Junhao Mu, Xiaoqian He, Bianfei Shao, Dishu Zhou, Weiyan Peng, Jun Tang, Yu Jiang, Guosheng Ren, Tingxiu Xiang
BACKGROUND: TET1 is a tumor suppressor gene (TSG) that codes for ten-eleven translocation methyl cytosine dioxygenase1 (TET1) catalyzing the conversion of 5-methylcytosine to 5-hydroxy methyl cytosine as a first step of TSG demethylation. Its hypermethylation has been associated with cancer pathogenesis. However, whether TET1 plays any role in nasopharyngeal carcinoma (NPC) remains unclear. This study investigated the expression and methylation of TET1 in NPC and confirmed its role and mechanism as a TSG...
August 3, 2018: Clinical Epigenetics
Catharine R Gale, Riccardo E Marioni, Sarah E Harris, John M Starr, Ian J Deary
BACKGROUND: The biological mechanisms underlying frailty in older people are poorly understood. There is some evidence to suggest that DNA methylation patterns may be altered in frail individuals. METHODS: Participants were 791 people aged 70 years from the Lothian Birth Cohort 1936. DNA methylation was measured in whole blood. Biological age was estimated using two measures of DNA methylation-based age acceleration-extrinsic and intrinsic epigenetic age acceleration...
August 3, 2018: Clinical Epigenetics
Aline Kaletsch, Maria Pinkerneil, Michèle J Hoffmann, Ananda A Jaguva Vasudevan, Chenyin Wang, Finn K Hansen, Constanze Wiek, Helmut Hanenberg, Christoph Gertzen, Holger Gohlke, Matthias U Kassack, Thomas Kurz, Wolfgang A Schulz, Günter Niegisch
BACKGROUND: Histone deacetylase inhibitors (HDACi) are promising anti-cancer drugs that could also be employed for urothelial carcinoma (UC) therapy. It is unclear, however, whether inhibition of all 11 zinc-dependent HDACs or of individual enzymes is more efficacious and specific. Here, we investigated the novel HDACi 19i (LMK235) with presumed preferential activity against class IIA HDAC4/5 in comparison to the pan-HDACi vorinostat (SAHA) and the HDAC4-specific HDACi TMP269 in UC cell lines with basal expression of HDAC4 and characterized two HDAC4-overexpressing UC cell lines...
July 31, 2018: Clinical Epigenetics
Nisreen Al-Moghrabi, Maram Al-Showimi, Nujoud Al-Yousef, Bushra Al-Shahrani, Bedri Karakas, Lamyaa Alghofaili, Hannah Almubarak, Safia Madkhali, Hind Al Humaidan
BACKGROUND: Constitutive methylation of tumor suppressor genes are associated with increased cancer risk. However, to date, the question of epimutational transmission of these genes remains unresolved. Here, we studied the potential transmission of BRCA1 and MGMT promoter methylations in mother-newborn pairs. METHODS: A total of 1014 female subjects (cancer-free women, n = 268; delivering women, n = 295; newborn females, n = 302; breast cancer patients, n = 67; ovarian cancer patients, n = 82) were screened for methylation status in white blood cells (WBC) using methylation-specific PCR and bisulfite pyrosequencing assays...
July 26, 2018: Clinical Epigenetics
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