'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Fri, 24 Jun 2016 04:19:49 PDT Fri, 24 Jun 2016 04:19:49 PDT jirtle@radonc.duke.edu james001@jirtle.com Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14. Martinez ME, Cox DF, Youth BP, Hernandez A
Eur J Hum Genet (Jun 2016)

Individuals with uniparental disomy of chromosome 14 (Temple and Kagami-Ogata syndromes) exhibit a number of developmental abnormalities originating, in part, from aberrant developmental expression of imprinted genes in the DLK1-DIO3 cluster. Although genomic imprinting has been reported in humans for some genes in the cluster, little evidence is available about the imprinting status of DIO3, which modulates developmental exposure to thyroid hormones. We used pyrosequencing to evaluate allelic expression of DLK1 and DIO3 in cDNAs prepared from neonatal foreskins carrying single-nucleotide polymorphisms (SNPs) in the exonic sequence of those genes, and hot-stop PCR to quantify DIO3 allelic expression in cDNA obtained from a skin specimen collected from an adult individual with known parental origin of the DIO3 SNP. In neonatal skin, DLK1 and DIO3 both exhibited a high degree of monoallelic expression from the paternal allele. In the adult skin sample, the allele preferentially expressed is that inherited from the mother, although a different, larger DIO3 mRNA transcript appears the most abundant at this stage. We conclude that DIO3 is an imprinted gene in humans, suggesting that alterations in thyroid hormone exposure during development may partly contribute to the phenotypes associated with uniparental disomy of chromosome 14.European Journal of Human Genetics advance online publication, 22 June 2016; doi:10.1038/ejhg.2016.66.]]>
Wed, 22 Jun 2016 00:00:00 PDT
De novo deciphering three-dimensional chromatin interaction and topological domains by wavelet transformation of epigenetic profiles. Chen Y, Wang Y, Xuan Z, Chen M, Zhang MQ
Nucleic Acids Res (Jun 2016)

Defining chromatin interaction frequencies and topological domains is a great challenge for the annotations of genome structures. Although the chromosome conformation capture (3C) and its derivative methods have been developed for exploring the global interactome, they are limited by high experimental complexity and costs. Here we describe a novel computational method, called CITD, for de novo prediction of the chromatin interaction map by integrating histone modification data. We used the public epigenomic data from human fibroblast IMR90 cell and embryonic stem cell (H1) to develop and test CITD, which can not only successfully reconstruct the chromatin interaction frequencies discovered by the Hi-C technology, but also provide additional novel details of chromosomal organizations. We predicted the chromatin interaction frequencies, topological domains and their states (e.g. active or repressive) for 98 additional cell types from Roadmap Epigenomics and ENCODE projects. A total of 131 protein-coding genes located near 78 preserved boundaries among 100 cell types are found to be significantly enriched in functional categories of the nucleosome organization and chromatin assembly. CITD and its predicted results can be used for complementing the topological domains derived from limited Hi-C data and facilitating the understanding of spatial principles underlying the chromosomal organization.]]>
Tue, 21 Jun 2016 00:00:00 PDT
Genome-Wide Discriminatory Information Patterns of Cytosine DNA Methylation. Sanchez R, Mackenzie SA
Int J Mol Sci (2016)

Cytosine DNA methylation (CDM) is a highly abundant, heritable but reversible chemical modification to the genome. Herein, a machine learning approach was applied to analyze the accumulation of epigenetic marks in methylomes of 152 ecotypes and 85 silencing mutants of Arabidopsis thaliana. In an information-thermodynamics framework, two measurements were used: (1) the amount of information gained/lost with the CDM changes I R and (2) the uncertainty of not observing a SNP L C R . We hypothesize that epigenetic marks are chromosomal footprints accounting for different ontogenetic and phylogenetic histories of individual populations. A machine learning approach is proposed to verify this hypothesis. Results support the hypothesis by the existence of discriminatory information (DI) patterns of CDM able to discriminate between individuals and between individual subpopulations. The statistical analyses revealed a strong association between the topologies of the structured population of Arabidopsis ecotypes based on I R and on LCR, respectively. A statistical-physical relationship between I R and L C R was also found. Results to date imply that the genome-wide distribution of CDM changes is not only part of the biological signal created by the methylation regulatory machinery, but ensures the stability of the DNA molecule, preserving the integrity of the genetic message under continuous stress from thermal fluctuations in the cell environment.]]>
Tue, 21 Jun 2016 00:00:00 PDT
Combinatorial epigenetic deregulation by Helicobacter pylori and Epstein-Barr virus infections in gastric tumourigenesis. Wu WK, Yu J, Chan MT, To KF, Cheng AS
J Pathol (Jul 2016)

Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodelling and microRNAs, convert environmental signals to transcriptional outputs but are commonly hijacked by pathogenic microorganisms. Recent advances in cancer epigenomics have shed new light on the importance of epigenetic deregulation in Helicobacter pylori- and Epstein-Barr virus (EBV)-driven gastric tumourigenesis. Moreover, it is becoming apparent that epigenetic mechanisms interact through crosstalk and feedback loops, which modify global gene expression patterns. The SWI/SNF remodelling complexes are commonly involved in gastric cancers associated with H. pylori or EBV through different mechanisms, including microRNA-mediated deregulation and genetic mutations. While H. pylori causes epigenetic silencing of tumour-suppressor genes to deregulate cellular pathways, EBV-positive tumours exhibit a widespread and distinctive DNA hypermethylation profile. Given the early successes of epigenetic drugs in haematological malignancies, further studies are mandated to enrich and translate our understanding of combinatorial epigenetic deregulation in gastric cancers into interventional strategies in the clinic. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.]]>
Tue, 21 Jun 2016 00:00:00 PDT
Targeted resequencing of regulatory regions at schizophrenia risk loci: Role of rare functional variants at chromatin repressive states. González-Peñas J, Amigo J, Santomé L, Sobrino B, Brenlla J, Agra S, Paz E, Páramo M, Carracedo Ã, Arrojo M, Costas J
Schizophr Res (Jul 2016)

There is mounting evidence that regulatory variation plays an important role in genetic risk for schizophrenia. Here, we specifically search for regulatory variants at risk by sequencing promoter regions of twenty-three genes implied in schizophrenia by copy number variant or genome-wide association studies. After strict quality control, a total of 55,206bp per sample were analyzed in 526 schizophrenia cases and 516 controls from Galicia, NW Spain, using the Applied Biosystems SOLiD System. Variants were filtered based on frequency from public databases, chromatin states from the RoadMap Epigenomics Consortium at tissues relevant for schizophrenia, such as fetal brain, mid-frontal lobe, and angular gyrus, and prediction of functionality from RegulomeDB. The proportion of rare variants at polycomb repressive chromatin state at relevant tissues was higher in cases than in controls. The proportion of rare variants with predicted regulatory role was significantly higher in cases than in controls (P=0.0028, OR=1.93, 95% C.I.=1.23-3.04). Combination of information from both sources led to the identification of an excess of carriers of rare variants with predicted regulatory role located at polycomb repressive chromatin state at relevant tissues in cases versus controls (P=0.0016, OR=19.34, 95% C.I.=2.45-2495.26). The variants are located at two genes affected by the 17q12 copy number variant, LHX1 and HNF1B. These data strongly suggest that a specific epigenetic mechanism, chromatin remodeling by histone modification during early development, may be impaired in a subset of schizophrenia patients, in agreement with previous data.]]>
Sat, 18 Jun 2016 00:00:00 PDT
Detection of differential DNA methylation in repetitive DNA of mice and humans perinatally exposed to bisphenol A. Faulk C, Kim JH, Anderson OS, Nahar MS, Jones TR, Sartor MA, Dolinoy DC
Epigenetics (Jun 2016)

Developmental exposure to bisphenol A (BPA) has been shown to induce changes in DNA methylation in both mouse and human genic regions; however, the response in repetitive elements and transposons has not been explored. Here we present novel methodology to combine genomic DNA enrichment with RepeatMasker analysis on next-generation sequencing data to determine the effect of perinatal BPA exposure on repetitive DNA at the class, family, subfamily, and individual insertion level in both mouse and human samples. Mice were treated during gestation and lactation to BPA in chow at 0, 50, or 50,000 ng/g levels and total BPA was measured in stratified human fetal liver tissue samples as low (non-detect to 0.83 ng/g), medium (3.5 to 5.79 ng/g), or high (35.44 to 96.76 ng/g). Transposon methylation changes were evident in human classes, families, and subfamilies, with the medium group exhibiting hypomethylation compared to both high and low BPA groups. Mouse repeat classes, families, and subfamilies did not respond to BPA with significantly detectable differential DNA methylation. In human samples, 1251 individual transposon loci were detected as differentially methylated by BPA exposure, but only 19 were detected in mice. Of note, this approach recapitulated the discovery of a previously known mouse environmentally labile metastable epiallele, Cabp(IAP). Thus, by querying repetitive DNA in both mouse and humans, we report the first known transposons in humans that respond to perinatal BPA exposure.]]>
Thu, 16 Jun 2016 00:00:00 PDT
Translation of genomics and epigenomics in prostate cancer: progress and promising directions. Liu W, Xu J
Asian J Androl (Jun 2016)

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Thu, 16 Jun 2016 00:00:00 PDT
Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm. Moreno-Romero J, Jiang H, Santos-González J, Köhler C
EMBO J (Jun 2016)

Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manuscript, we have addressed the key question whether parentally inherited differential DNA methylation affects de novo targeting of chromatin modifiers in the early endosperm. Our data reveal that polycomb-mediated H3 lysine 27 trimethylation (H3K27me3) is preferentially localized to regions that are targeted by the DNA glycosylase DEMETER (DME), mechanistically linking DNA hypomethylation to imprinted gene expression. Our data furthermore suggest an absence of de novo DNA methylation in the early endosperm, providing an explanation how DME-mediated hypomethylation of the maternal genome is maintained after fertilization. Lastly, we show that paternal-specific H3K27me3-marked regions are located at pericentromeric regions, suggesting that H3K27me3 and DNA methylation are not necessarily exclusive marks at pericentromeric regions in the endosperm.]]>
Thu, 16 Jun 2016 00:00:00 PDT
The importance of detailed epigenomic profiling of different cell types within organs. Stueve TR, Marconett CN, Zhou B, Borok Z, Laird-Offringa IA
Epigenomics (Jun 2016)

The human body consists of hundreds of kinds of cells specified from a single genome overlaid with cell type-specific epigenetic information. Comprehensively profiling the body's distinct epigenetic landscapes will allow researchers to verify cell types used in regenerative medicine and to determine the epigenetic effects of disease, environmental exposures and genetic variation. Key marks/factors that should be investigated include regions of nucleosome-free DNA accessible to regulatory factors, histone marks defining active enhancers and promoters, DNA methylation levels, regulatory RNAs, and factors controlling the three-dimensional conformation of the genome. Here we use the lung to illustrate the importance of investigating an organ's purified cell epigenomes, and outline the challenges and promise of realizing a comprehensive catalog of primary cell epigenomes.]]>
Wed, 15 Jun 2016 00:00:00 PDT
Pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA or histone modification H3K9Me3. Rasmussen L, Herzog M, Rømer E, Micallef J, Bulut O, Wilhelmsen M, Christensen IJ, Nielsen HJ
Scand J Clin Lab Invest (Jun 2016)

To evaluate pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA (5mC) or histone modification H3K9Me3 (H3K9Me3).]]>
Mon, 13 Jun 2016 00:00:00 PDT
Data Management for Heterogeneous Genomic Datasets. Ceri S, Kaitoua A, Masseroli M, Pinoli P, Venco F
IEEE/ACM Trans Comput Biol Bioinform (Jun 2016)

Next Generation Sequencing (NGS), a family of technologies for reading the DNA and RNA, is changing biological research, and will soon change medical practice, by quickly providing sequencing data and high-level features of numerous individual genomes in different biological and clinical conditions. Availability of millions of whole genome sequences may soon become the biggest and most important "big data" problem of mankind. In this exciting framework, we recently proposed a new paradigm to raise the level of abstraction in NGS data management, by introducing a GenoMetric Query Language (GMQL) and demonstrating its usefulness through several biological query examples. Leveraging on that effort, here we motivate and formalize GMQL operations, especially focusing on the most characteristic and domain-specific ones. Furthermore, we address their efficient implementation and illustrate the architecture of the new software system that we have developed for their execution on big genomic data in a cloud computing environment, providing the evaluation of its performance. The new system implementation is available for download at the GMQL website (http://www.bioinformatics.deib.polimi.it/GMQL/); GMQL can also be tested through a set of predefined queries on ENCODE and Roadmap Epigenomics data at http://www.bioinformatics.deib.polimi.it/GMQL/queries/.]]>
Mon, 13 Jun 2016 00:00:00 PDT
Drug metabolism and disposition diversity of Ranunculales phytometabolites: A systems perspective. Hao DC, Yang L
Expert Opin Drug Metab Toxicol (Jun 2016)

Although investigations in metabolism and pharmacokinetics of Ranunculales phytometabolites are booming, data obtained from human and animal studies have not been summarized as a whole to outline current trends and to predict future development.]]>
Mon, 13 Jun 2016 00:00:00 PDT
Endosperm turgor pressure decreases during early Arabidopsis seed development. Beauzamy L, Fourquin C, Dubrulle N, Boursiac Y, Boudaoud A, Ingram G
Development (Jun 2016)

In Arabidopsis, rapid expansion of the coenocytic endosperm after fertilization has been proposed to drive early seed growth, which is in turn constrained by the seed coat. This hypothesis implies physical heterogeneity between the endosperm and seed coat compartments during early seed development, which to date has not been demonstrated. Here we combine tissue indentation with modelling to show that the physical properties of the developing seed are consistent with the hypothesis that elevated endosperm-derived turgor pressure drives early seed expansion. We provide evidence that whole-seed turgor is generated by the endosperm at early developmental stages. Furthermore, we show that endosperm cellularization and seed growth arrest are associated with a drop in endosperm turgor pressure. Finally we demonstrated that this decrease is perturbed when the function of POLYCOMB REPRESSIVE COMPLEX2 is lost, suggesting that turgor pressure changes could be a target of genomic imprinting. Our results indicate a developmental role for changes in endosperm turgor-pressure in the Arabidopsis seed.]]>
Sat, 11 Jun 2016 00:00:00 PDT
Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research. Maes M, Nowak G, Caso JR, Leza JC, Song C, Kubera M, Klein H, Galecki P, Noto C, Glaab E, Balling R, Berk M
Mol Neurobiol (Jul 2016)

Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.]]>
Sat, 11 Jun 2016 00:00:00 PDT
Toward Systems Understanding of Leaf Senescence: An Integrated Multi-Omics Perspective on Leaf Senescence Research. Kim J, Woo HR, Nam HG
Mol Plant (Jun 2016)

Leaf senescence is a complex but tightly regulated developmental process involving a coordinated sequence of multiple molecular events, which ultimately leads to death of the leaf. Efforts to understand the mechanistic principles underlying leaf senescence have been largely made by transcriptomic, proteomic, and metabolomic studies over the past decade. This review focuses on recent milestones in leaf senescence research obtained using multi-omics technologies, as well as future endeavors toward systems understanding of leaf senescence processes. In particular, we discuss recent advances in understanding molecular events during leaf senescence through genome-wide transcriptome analyses in Arabidopsis. We also describe comparative transcriptome analyses used to unveil the commonality and diversity of regulatory mechanisms governing leaf senescence in the plant kingdom. Finally, we provide current illustrations of epigenomic, proteomic, and metabolomic landscapes of leaf senescence. We envisage that integration of multi-omics leaf senescence data will enable us to address unresolved questions regarding leaf senescence, including determining the molecular principles that coordinate concurrent and ordered changes in biological events during leaf senescence.]]>
Thu, 09 Jun 2016 00:00:00 PDT
Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis. Hu Z, Jiang K, Frank MB, Chen Y, Jarvis JN
Sci Rep (2016)

NIH projects such as ENCODE and Roadmap Epigenomics have revealed surprising complexity in the transcriptomes of mammalian cells. In this study, we explored transcriptional complexity in human neutrophils, cells generally regarded as nonspecific in their functions and responses. We studied distinct human disease phenotypes and found that, at the gene, gene isoform, and miRNA level, neutrophils exhibit considerable specificity in their transcriptomes. Thus, even cells whose responses are considered non-specific show tailoring of their transcriptional repertoire toward specific physiologic or pathologic contexts. We also found that miRNAs had a global impact on neutrophil transcriptome and are associated with innate immunity in juvenile idiopathic arthritis (JIA). These findings have important implications for our understanding of the link between genes, non-coding transcripts and disease phenotypes.]]>
Thu, 09 Jun 2016 00:00:00 PDT
H19ICR mediated transcriptional silencing does not require target promoter methylation. Gebert C, Rong Q, Jeong S, Iben J, Pfeifer K
Biochem Biophys Res Commun (Jul 2016)

Transcription of the reciprocally imprinted genes Insulin-like growth factor 2 (Igf2) and H19 is orchestrated by the 2.4-kb H19 Imprinting Control Region (H19ICR) located upstream of H19. Three known functions are associated with the H19ICR: (1) it is a germline differentially methylated region, (2) it is a transcriptional insulator, and (3) it is a transcriptional silencer. The molecular mechanisms of the DMR and insulator functions have been well characterized but the basis for the ICR's silencer function is less well understood. In order to study the role the H19ICR intrinsically plays in gene silencing, we transferred the 2.4-kb H19ICR to a heterologous non-imprinted location on chromosome 5, upstream of the alpha fetoprotein (Afp) promoter. Independent of its orientation, the 2.4-kb H19ICR silences transcription from the paternal Afp promoter. Thus silencing is a function intrinsic to this DNA element. Further, ICR mediated silencing is a developmental process that, unexpectedly, does not occur through DNA methylation at the target promoter.]]>
Mon, 06 Jun 2016 00:00:00 PDT
Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine. Ogino S, Nishihara R, VanderWeele TJ, Wang M, Nishi A, Lochhead P, Qian ZR, Zhang X, Wu K, Nan H, Yoshida K, Milner DA, Chan AT, Field AE, Camargo CA, Williams MA, Giovannucci EL
Epidemiology (Jul 2016)

Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public health.]]>
Sat, 04 Jun 2016 00:00:00 PDT
Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Reece AS, Hulse GK
Mutat Res (Jul 2016)

The recent demonstration that massive scale chromosomal shattering or pulverization can occur abruptly due to errors induced by interference with the microtubule machinery of the mitotic spindle followed by haphazard chromosomal annealing, together with sophisticated insights from epigenetics, provide profound mechanistic insights into some of the most perplexing classical observations of addiction medicine, including cancerogenesis, the younger and aggressive onset of addiction-related carcinogenesis, the heritability of addictive neurocircuitry and cancers, and foetal malformations. Tetrahydrocannabinol (THC) and other addictive agents have been shown to inhibit tubulin polymerization which perturbs the formation and function of the microtubules of the mitotic spindle. This disruption of the mitotic machinery perturbs proper chromosomal segregation during anaphase and causes micronucleus formation which is the primary locus and cause of the chromosomal pulverization of chromothripsis and downstream genotoxic events including oncogene induction and tumour suppressor silencing. Moreover the complementation of multiple positive cannabis-cancer epidemiological studies, and replicated dose-response relationships with established mechanisms fulfils causal criteria. This information is also consistent with data showing acceleration of the aging process by drugs of addiction including alcohol, tobacco, cannabis, stimulants and opioids. THC shows a non-linear sigmoidal dose-response relationship in multiple pertinent in vitro and preclinical genotoxicity assays, and in this respect is similar to the serious major human mutagen thalidomide. Rising community exposure, tissue storage of cannabinoids, and increasingly potent phytocannabinoid sources, suggests that the threshold mutagenic dose for cancerogenesis will increasingly be crossed beyond the developing world, and raise transgenerational transmission of teratogenicity as an increasing concern.]]>
Mon, 30 May 2016 00:00:00 PDT
Association of interleukin-6 methylation in leukocyte DNA with serum level and the risk of ischemic heart disease. Yang Q, Zhao Y, Zhang Z, Chen J
Scand J Clin Lab Invest (Jul 2016)

Background Interleukin-6 (IL-6), a multifunctional cytokine, plays an important role in the development of ischemic heart disease (IHD), and DNA hypomethylation of 2 CpGs, located downstream in the proximity of the IL-6 gene promoter, has been associated with risk factor for IHD. This study was to examine the association of blood leukocyte DNA methylation of the 2 CpGs in IL-6 with the risk of IHD and the serum IL-6 level. Methods IL-6 methylation levels of 582 cases and 673 controls were measured using the bisulfite pyrosequencing technology. Serum level of IL-6 was measured using enzyme-linked immunosorbent assay. Results The IL-6 methylation was significantly lower in IHD cases than in the controls, irrespective of CpG site. After multivariate adjustment, lower (< median) average IL-6 methylation was associated with an increased risk of IHD (OR 1.57, 95% CI 1.22-2.02, p < 0.001). Average IL-6 methylation level was inversely associated with serum IL-6 level (β = -1.02 pg/mL per increase in IL-6 methylation, p = 0.002) among IHD cases. This significant relationship was not observed among controls. Conclusions DNA hypomethylation of IL-6 gene measured in blood leukocytes was associated with increased risk of IHD. IL-6 demethylation may upregulate its expression, whereby exerting its risk effect on the development of IHD.]]>
Fri, 13 May 2016 00:00:00 PDT