Clinical Epigenetics

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

List of Papers (Total 586)

Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue

Background DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have...

Epigenetic changes in blood leukocytes following an omega-3 fatty acid supplementation

Background Omega-3 polyunsaturated fatty acids (n-3 FAs) have several beneficial effects on cardiovascular (CV) disease risk factors. These effects on CV risk profile may be mediated by several factors, including epigenetic modifications. Our objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in...

Circulating unmethylated insulin DNA as a potential non-invasive biomarker of beta cell death in type 1 Diabetes: a review and future prospect

BackgroundThe early detection of type 1 diabetes (T1D) largely depends on a reliable approach to monitor β cell loss. An effective way to evaluate the decline of β cell mass would allow early preventative intervention to preserve insulin secretion.Main bodyRecent progress in the development of novel biomarkers, based on tissue-specific methylation patterns, has inspired relevant...

Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD

Background Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) regulate goblet cell differentiation. This study aimed to (1...

Epigenetic assays for chemical biology and drug discovery

The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including...

Cord blood hematopoietic cells from preterm infants display altered DNA methylation patterns

Background Premature infants are highly vulnerable to infection. This is partly attributable to the preterm immune system, which differs from that of the term neonate in cell composition and function. Multiple studies have found differential DNA methylation (DNAm) between preterm and term infants’ cord blood; however, interpretation of these studies is limited by the confounding...

36 h fasting of young men influences adipose tissue DNA methylation of LEP and ADIPOQ in a birth weight-dependent manner

Background Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short...

DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD

Background Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation...

Differential adipokine DNA methylation and gene expression in subcutaneous adipose tissue from adult offspring of women with diabetes in pregnancy

Background Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic...

Clusterization in head and neck squamous carcinomas based on lncRNA expression: molecular and clinical correlates

Background Long non-coding RNAs (lncRNAs) have emerged as key players in a remarkably variety of biological processes and pathologic conditions, including cancer. Next-generation sequencing technologies and bioinformatics procedures predict the existence of tens of thousands of lncRNAs, from which we know the functions of only a handful of them, and very little is known in cancer...

DNA methylation signatures for 2016 WHO classification subtypes of diffuse gliomas

Background Glioma is the most common of all primary brain tumors with poor prognosis and high mortality. The 2016 World Health Organization classification of the tumors of central nervous system uses molecular parameters in addition to histology to redefine many tumor entities. The new classification scheme divides diffuse gliomas into low-grade glioma (LGG) and glioblastoma (GBM...

Assessing alternative base substitutions at primer CpG sites to optimise unbiased PCR amplification of methylated sequences

Background Determining the role of DNA methylation in various biological processes is dependent on the accurate representation of often highly complex patterns. Accurate representation is dependent on unbiased PCR amplification post bisulfite modification, regardless of methylation status of any given epiallele. This is highly dependent on primer design. Particular difficulties...

Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities

Aberrant DNA methylation is an epigenetic hallmark of melanoma, known to play important roles in melanoma formation and progression. Recent advances in genome-wide methylation methods have provided the means to identify differentially methylated genes, methylation signatures, and potential biomarkers. However, despite considerable effort and advances in cataloging methylation...

Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours

DNA methylation is the most studied epigenetic modification due to its role in regulating gene expression, and its involvement in the pathogenesis of cancer and several diseases upon aberrations in methylation. The method of choice to evaluate genome-wide methylation has been the Illumina HumanMethylation450 BeadChip (450K), but it was recently replaced with the MethylationEPIC...

Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk—an exploratory study

BackgroundPrenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that...

Epigenetic signatures of gestational diabetes mellitus on cord blood methylation

Background Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal...

A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours

Background Dysregulation in post-translational modifications of histones and their modifiers are now well-recognized as a hallmark of cancer and can be used as biomarkers and potential therapeutic targets for disease progression and prognosis. In most solid tumours, a biopsy is challenging, costly, painful or potentially risky for the patient. Therefore, non-invasive methods like...

Associations of LEP, CRH, ICAM-1, and LINE-1 methylation, measured in saliva, with waist circumference, body mass index, and percent body fat in mid-childhood

BackgroundGenetics explains a small proportion of variance in body mass index at the population level. Epigenetics, commonly measured by gene methylation, holds promise for understanding obesity risk factors and mechanisms.MethodsParticipants were 431 adolescents aged 10–15 years. BMI z-score, waist circumference z-score, and percent body fat were measured. Saliva samples were...

The dynamic DNA methylation landscape of the mutL homolog 1 shore is altered by MLH1-93G>A polymorphism in normal tissues and colorectal cancer

Background Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 (MLH1), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1...

LINE-1 is preferentially hypomethylated within adenomatous polyps in the presence of synchronous colorectal cancer

Background Conventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC). Whether features of adenomas could serve as predictors of synchronous CRC is not known. Here, we investigate whether global methylation markers, including LINE-1, differ within...

Epigenome-wide discovery and evaluation of leukocyte DNA methylation markers for the detection of colorectal cancer in a screening setting

BackgroundColorectal cancer (CRC) is the third most common cancer worldwide. If detected at an early stage, prognosis is good. Despite increasing evidence for the benefits of implemented screening programs, such as screening colonoscopy, compliance is rather low. Hence there is demand for non-invasive tests for the early detection of CRC with high acceptance in population-wide...

Cerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: the atherosclerosis risk in communities study

Background Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are part of the spectrum of brain vascular injury accompanying aging and are associated with a substantial risk of stroke and dementia. We investigated the association of cerebral WMH burden on MRI with a DNA methylation-based biomarker of aging, termed DNA methylation age acceleration...

Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals

Background Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also...