Clinical Epigenetics

http://link.springer.com/journal/13148

List of Papers (Total 586)

Maternal eating disorders affect offspring cord blood DNA methylation: a prospective study

BackgroundEating disorders (ED) are chronic psychiatric disorders, common amongst women of reproductive age. ED in pregnancy are associated with poor nutrition and abnormal intrauterine growth. Increasing evidence also shows offspring of women with ED have adverse developmental and birth outcomes. We sought to carry out the first study investigating DNA methylation in offspring...

Methods and novel technology for microRNA quantification in colorectal cancer screening

The screening and diagnosis of colorectal cancer (CRC) currently relies heavily on invasive endoscopic techniques as well as imaging and antigen detection tools. More accessible and reliable biomarkers are necessary for early detection in order to expedite treatment and improve patient outcomes. Recent studies have indicated that levels of specific microRNA (miRNA) are altered in...

Performance of a methylation specific real-time PCR assay as a triage test for HPV-positive women

BackgroundHPV DNA testing as a primary screening marker is being implemented in several countries. Due to the high HPV prevalence in the screening population, effective triage strategies for HPV-positive cases are required. The aim of this study was to evaluate the performance of a methylation-specific real-time PCR  assay (GynTect®) comprising six marker regions as a triage test...

Turnover of histones and histone variants in postnatal rat brain: effects of alcohol exposure

Background Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental health problems to poor social adjustment and stress tolerance...

Silencing HOXD10 by promoter region hypermethylation activates ERK signaling in hepatocellular carcinoma

Background Hepatocellular carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Dysregulation of HomeoboxD10 (HOXD10) was found to suppress or promote cancer progression in different cancer types. The function and regulation of HOXD10 remain unclear in human hepatocellular carcinoma (HCC). Methods Primary HCC samples (117...

Methylation of ZNF331 is an independent prognostic marker of colorectal cancer and promotes colorectal cancer growth

Background ZNF331 was reported to be a transcriptional repressor. Methylation of the promoter region of ZNF331 has been found frequently in human esophageal and gastric cancers. The function and methylation status of ZNF331 remain to be elucidated in human colorectal cancer (CRC). Methods Six colorectal cancer cell lines, 146 cases of primary colorectal cancer samples, and 10...

Identification of a key role of widespread epigenetic drift in Barrett’s esophagus and esophageal adenocarcinoma

Background Recent studies have identified age-related changes in DNA methylation patterns in normal and cancer tissues in a process that is called epigenetic drift. However, the evolving patterns, functional consequences, and dynamics of epigenetic drift during carcinogenesis remain largely unexplored. Here we analyze the evolution of epigenetic drift patterns during progression...

MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer

Background Multiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities. Results Herein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis...

Epigenome-wide association study of asthma and wheeze in childhood and adolescence

Background Asthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis. Methods Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation...

Effect of a diet containing folate and hazelnut oil capsule on the methylation level of the ADRB3 gene, lipid profile and oxidative stress in overweight or obese women

Background Studies of genes that play an important role in the development of obesity are needed, especially studies focusing on genes that regulate food intake and affect nutrient metabolism. For example, the beta-3 adrenergic receptor (ADRB3) responds to noradrenaline and mediates lipolysis in adipocytes. Methods This was a controlled intervention study involving 40 overweight...

Mosaic genome-wide maternal isodiploidy: an extreme form of imprinting disorder presenting as prenatal diagnostic challenge

Background Uniparental disomy of certain chromosomes are associated with a group of well-known genetic syndromes referred to as imprinting disorders. However, the extreme form of uniparental disomy affecting the whole genome is usually not compatible with life, with the exception of very rare cases of patients with mosaic genome-wide uniparental disomy reported in the literature...

Promoter methylation inhibits expression of tumor suppressor KIBRA in human clear cell renal cell carcinoma

Background KIBRA has been suggested as a key regulator of the Hippo signaling pathway, regulating organ size, cell contact inhibition, tissue regeneration as well as tumorigenesis and cystogenesis. We recently reported that human KIBRA expression depends on a complex alternative CpG-rich promoter system. Our current study aimed at the identification of epigenetic mechanisms...

Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1

Background There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach. Methods We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to...

A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML

Background Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in...

DNA methylation links genetics, fetal environment, and an unhealthy lifestyle to the development of type 2 diabetes

Type 2 diabetes is a complex trait with both environmental and hereditary factors contributing to the overall pathogenesis. One link between genes, environment, and disease is epigenetics influencing gene transcription and, consequently, organ function. Genome-wide studies have shown altered DNA methylation in tissues important for glucose homeostasis including pancreas, liver...

Epigenome alterations in aortic valve stenosis and its related left ventricular hypertrophy

Aortic valve stenosis is the most common cardiac valve disease, and with current trends in the population demographics, its prevalence is likely to rise, thus posing a major health and economic burden facing the worldwide societies. Over the past decade, it has become more than clear that our traditional genetic views do not sufficiently explain the well-known link between AS...

Identification and characterization of interferon signaling-related microRNAs in occult hepatitis B virus infection

Background Occult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. However, the characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. Therefore, this study aimed to analyze the...

Diabetes medication associates with DNA methylation of metformin transporter genes in the human liver

Background Given that metformin is the most common pharmacological therapy for type 2 diabetes, understanding the function of this drug is of great importance. Hepatic metformin transporters are responsible for the pharmacologic action of metformin. However, epigenetics in genes encoding metformin transporters has not been fully elucidated. We examined the DNA methylation of...

Down-regulation of MBD4 contributes to hypomethylation and overexpression of CD70 in CD4+ T cells in systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by lymphocytic infiltration and overproduction of autoantibodies, leading to significant morbidity and mortality. However, the pathogenesis of this disorder has not yet been completely elucidated. It has been reported that CD70, a B cell costimulatory molecule encoded by the gene TNFSF7...

An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study

BackgroundEpigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub-Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of adiposity among Ghanaians aiming to identify DNA methylation loci that are significantly...

DNA hypomethylation of a transcription factor binding site within the promoter of a gout risk gene NRBP1 upregulates its expression by inhibition of TFAP2A binding

Background Genome-wide association studies (GWASs) have identified dozens of loci associated with gout, but for most cases, the risk genes and the underlying molecular mechanisms contributing to these associations are unknown. This study sought to understand the molecular mechanism of a common genetic variant, rs780093, in the development of gout, both in vitro and in vivo...

Epigenetic clocks for gestational age: statistical and study design considerations

In this letter to the editor, we highlight some concerns with a recently published method to estimate gestational age at delivery from DNA methylation data. We conduct novel analyses to highlight the implications of different choices in study design and statistical methods for the prediction of phenotypes from methylation data.

Histone code and long non-coding RNAs (lncRNAs) aberrations in lung cancer: implications in the therapy response

Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or...

Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients

Background Patients with early colorectal cancer (stages I–II) generally have a good prognosis, but a subgroup of 15–20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early...

Efficacy of EZH2 inhibitory drugs in human papillomavirus-positive and human papillomavirus-negative oropharyngeal squamous cell carcinomas

Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with rates of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) dramatically increasing. The overexpression of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for the trimethylation at lysine 27 of histone 3 (H3K27me3), is associated with a...