Clinical Epigenetics

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

List of Papers (Total 602)

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...

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

BackgroundDecitabine 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 children...

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

BackgroundThere 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.MethodsWe selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to...

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...

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...

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

BackgroundGiven 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 these...

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...

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...

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

BackgroundPatients 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...

Epigenetic regulation of inflammation in localized aggressive periodontitis

Background We have previously demonstrated a Toll-like receptor (TLR)-mediated hyper-responsive phenotype in our cohort of localized aggressive periodontitis (LAP) individuals. However, mechanisms related to this phenotype are still not clear in the literature. The objective of this cross-sectional study is to examine the role of epigenetic regulation, specifically DNA...

Alterations of sorbin and SH3 domain containing 3 (SORBS3) in human skeletal muscle following Roux-en-Y gastric bypass surgery

Background Obesity is a disease that is caused by genetic and environmental factors. However, epigenetic mechanisms of obesity are less well known. DNA methylation provides a mechanism whereby environmental factors can influence gene transcription. The aim of our study was to investigate skeletal muscle DNA methylation of sorbin and SH3 domain containing 3 (SORBS3) with weight...

Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome

Background Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified. Results To address whether epigenetic changes can be associated with Werner...

Pyrosequencing quantified methylation level of miR-124 predicts shorter survival for patients with myelodysplastic syndrome

Background Aberrant CpG island methylation has been increasingly recognized as a common event in myelodysplastic syndrome (MDS). To date, most of the previous studies of miR-124 in MDS have focused on epigenetic changes and little is known about the underlying mechanism through which miR-124 regulates CDK6 expression. Results In the present study, we employed pyrosequencing...

The association between Alu hypomethylation and severity of type 2 diabetes mellitus

Background Cellular senescence due to genomic instability is believed to be one of the mechanisms causing health problems in diabetes mellitus (DM). Low methylation levels of Alu elements or Alu hypomethylation, an epigenomic event causing genomic instability, were commonly found in aging people and patients with aging phenotypes, such as osteoporosis. Results We investigate Alu...

Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma

Background DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. Methods A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas...

Epigenetic response of imprinted domains during carcinogenesis

Background Imprinted domains have been identified as targets for aberrant DNA methylation during carcinogenesis, but it remains unclear when these epigenetic alterations occur and how they contribute to tumor progression. Epigenetic instability at key cis-regulatory elements within imprinted domains can concomitantly activate proto-oncogenes and turn off tumor suppressor genes...

The effect of Nipped-B-like (Nipbl) haploinsufficiency on genome-wide cohesin binding and target gene expression: modeling Cornelia de Lange syndrome

Background Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder frequently associated with heterozygous loss-of-function mutations of Nipped-B-like (NIPBL), the human homolog of Drosophila Nipped-B. NIPBL loads cohesin onto chromatin. Cohesin mediates sister chromatid cohesion important for mitosis but is also increasingly recognized as a regulator of gene...

Cord blood DNA methylation and adiposity measures in early and mid-childhood

Background Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strategies to prevent the onset of the condition. We performed an epigenome-wide association study to prospectively investigate the relationship between cord blood DNA...