Abstract:
BACKGROUND:As a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohn's disease (CD) and is especially pertinent to early onset disease. METHODS:The Illumina 450K platform was applied to assess epigenome-wide methylation profiles in circulating leukocyte DNA in discovery and replication pediatric CD cohorts and controls. Data were corrected for differential leukocyte proportions. Targeted replication was performed in adults using pyrosequencing. Methylation changes were correlated with gene expression in blood and intestinal mucosa. RESULTS:We identified 65 individual CpG sites with methylation alterations achieving epigenome-wide significance after Bonferroni correction (P < 1.1 × 10(-7)), and 19 differently methylated regions displaying unidirectional methylation change. There was a highly significant enrichment of methylation changes around GWAS single nucleotide polymorphisms (P = 3.7 × 10(-7)), notably the HLA region and MIR21. Two-locus discriminant analysis in the discovery cohort predicted disease in the pediatric replication cohort with high accuracy (area under the curve, 0.98). The findings strongly implicate the transcriptional start site of MIR21 as a region of extended epigenetic alteration, containing the most significant individual probes (P = 1.97 × 10(-15)) within a GWAS risk locus. In extension studies, we confirmed hypomethylation of MIR21 in adults (P = 6.6 × 10(-5), n = 172) and show increased mRNA expression in leukocytes (P < 0.005, n = 66) and in the inflamed intestine (P = 1.4 × 10(-6), n = 99). CONCLUSIONS:We demonstrate highly significant and replicable differences in DNA methylation in CD, defining the disease-associated epigenome. The data strongly implicate known GWAS loci, with compelling evidence implicating MIR21 and the HLA region.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Adams AT,Kennedy NA,Hansen R,Ventham NT,OʼLeary KR,Drummond HE,Noble CL,El-Omar E,Russell RK,Wilson DC,Nimmo ER,Hold GL,Satsangi Jdoi
10.1097/MIB.0000000000000179subject
Has Abstractpub_date
2014-10-01 00:00:00pages
1784-93issue
10eissn
1078-0998issn
1536-4844journal_volume
20pub_type
杂志文章abstract:BACKGROUND:A North American genome-wide single nucleotide polymorphism (SNP) association study identified IL23R as a novel inflammatory bowel disease (IBD) susceptibility gene. Association was reported with multiple risk variants in the centromeric portion of IL23R in 3 large independent cohorts. The aims of this study...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20180
更新日期:2007-09-01 00:00:00
abstract:Backgrounds:We sought to describe the outcomes of endoscopic therapy of luminal strictures in patients with Crohn's disease (CD) at a large tertiary referral center. Methods:All patients who had undergone endoscopic dilation of CD strictures between January 1, 1990 and November 30, 2013 were identified. Demographics, ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy049
更新日期:2018-06-08 00:00:00
abstract::: Patients with ulcerative colitis are at increased risk for colorectal adenocarcinoma compared with the general population. Although surveillance for colorectal malignancy and dysplasia (a premalignant lesion) has been recommended, a benefit in reducing mortality from colorectal cancer via surveillance or prophylacti...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract:BACKGROUND:Children with inflammatory bowel disease (IBD) undergo imaging using ionizing radiation and may be exposed to high cumulative radiation. We hypothesized that children with IBD have high exposure to radiation from medical imaging. METHODS:An Institutional Review Board (IRB)-approved retrospective chart revie...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21626
更新日期:2011-11-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel diseases (IBD) are characterized by intermittent relapses, and their course is heterogeneous and unpredictable. Our aim was to determine the ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease. METHODS:This prospective study enroll...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa183
更新日期:2020-09-18 00:00:00
abstract:BACKGROUND:The dinitrofluorobenzene/dinitrosulfonic acid (DNFB/DNS) model was originally described as an experimental model of intestinal inflammation resembling human ulcerative colitis (UC). Due to the absence of acceptable UC experimental models for pharmacological preclinical assays, here we examine the immune resp...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21586
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Data from CHARM, a 56-week, randomized controlled trial of adalimumab for patients with moderately to severely active Crohn's disease (CD), were used to evaluate outcomes of adalimumab dosage adjustment. METHODS:Patients randomized to blinded adalimumab 40 mg every other week (EOW) in CHARM were the focus o...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
doi:10.1002/ibd.21328
更新日期:2011-01-01 00:00:00
abstract::The conventional treatment of inflammatory bowel disease (IBD) has focused on nonspecifically targeting mucosal inflammation. In the last decade, with the advent of novel biological agents that directly inhibit proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), rapid progress has been made in clin...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.21336
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Outcomes are suboptimal in ulcerative colitis (UC). Telemedicine for UC is feasible and improves outcomes. Our goals were to evaluate a home telemanagement system for UC (UC HAT) on disease activity, quality of life (QoL), and adherence compared to best available care (BAC) in a randomized, controlled trial....
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
doi:10.1002/ibd.21795
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Portal vein thrombosis (PVT) is a poorly described complication of inflammatory bowel disease (IBD). We sought to better characterize presentations, compare treatments, and assess outcomes in IBD-related PVT. METHODS:We conducted a retrospective investigation of IBD-related PVT at our institution. Multivari...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izaa053
更新日期:2021-01-19 00:00:00
abstract:BACKGROUND:Although magnetic resonance imaging (MRI) is an increasingly used diagnostic tool in the assessment of inflammatory bowel disease (IBD) in humans, diagnosis and quantitation of intestinal inflammation in animal models of IBD still depends on ex vivo techniques. The aim of this study was to evaluate whether h...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.23006
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Unlike other anti-tumor necrosis factor alpha antibodies, golimumab does not deliver on its promise of effectiveness for treating patients with ulcerative colitis. We investigated the value of therapeutic drug monitoring for optimizing golimumab therapy. METHODS:We analyzed the golimumab pharmacokinetics da...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz144
更新日期:2020-03-04 00:00:00
abstract::The risk of colorectal cancer in patients with long-standing ulcerative colitis or colonic Crohn's disease is increased. Patients with long-standing ulcerative colitis are offered enrollment into programs of endoscopic surveillance. Although direct evidence for a protective effect of surveillance against death from co...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0b013e3182802c6a
更新日期:2013-03-01 00:00:00
abstract::Inflammatory bowel disease (IBD) is now recognized as a common chronic disease affecting children and adolescents. This article will review recent advances made in the fields of genetics, epidemiology, gut ecology, and immunology regarding the etiopathogenesis of IBD, with particular emphasis on the contributions made...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/00054725-200203000-00008
更新日期:2002-03-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) develops in ulcerative colitis (UC) and Crohn's disease. However, there is scarce reporting on the onset of UC in patients with NAFLD. A 44-year-old man was diagnosed with UC and referred to us in 2019. His height was 166.0 cm, and body weight was 86.3 kg. The waist circumferen...
journal_title:Inflammatory bowel diseases
pub_type: 信件
doi:10.1093/ibd/izz208
更新日期:2019-10-18 00:00:00
abstract:BACKGROUND:The clinical course of ulcerative colitis (UC) is unpredictable. During recent years, the ability of fecal biomarkers to predict relapse in inflammatory bowel disease has been evaluated. The objective of this study was to assess fecal calprotectin (FC) as a predictor of disease recurrence in patients with ne...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1097/MIB.0b013e31827e78be
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Extracellular nucleotides released in conditions of cell stress alert the immune system from tissue injury or inflammation. We hypothesized that the P2X7 receptor (P2X7-R) could regulate key elements in inflammatory bowel disease pathogenesis. METHODS:Colonoscopy samples obtained from patients with Crohn's ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000441201.10454.06
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Host-microbe interactions at the intestinal mucosal-luminal interface (MLI) are critical factors in the biology of inflammatory bowel disease (IBD). METHODS:To address this issue, we performed a series of investigations integrating analysis of the bacteria and metaproteome at the MLI of Crohn's disease, ulc...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21793
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Extraintestinal manifestations of Crohn's disease (CD) have not previously included the central nervous system (CNS). Restless legs syndrome (RLS) is a CNS disorder that is either idiopathic or secondary to a number of diseases. The aim of this study was to determine if RLS was associated with CD because bot...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20992
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Mucosal healing (MH) is associated with improved clinical outcomes in patients with Crohn's disease (CD) and ulcerative colitis (UC). MH as a target for treatment has been suggested, although there is little pediatric data. The goal of this study was to evaluate MH in clinical practice in pediatric patients ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
doi:10.1097/MIB.0000000000001176
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:The pathophysiological basis for corticosteroid (CS) failure in ulcerative colitis (UC) is unknown. A transactivation glucocorticoid bioassay (GBA) was developed to measure the biological activity of CS by quantifying glucocorticoid response elements. This approach eliminates differences in bioavailability, ...
journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/ibd.21070
更新日期:2010-03-01 00:00:00
abstract:Background:Suicide is a leading cause of death worldwide. Transition from suicidal ideation (SI) to suicide attempt is high within a year of SI onset. The risk of suicide and SI is elevated in persons with inflammatory bowel disease (IBD) versus the general population. We aimed to validate the Patient Heath Questionnai...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy032
更新日期:2018-07-12 00:00:00
abstract::Germ-free (GF) interleukin 10-deficient (IL-10) mice develop chronic colitis after colonization by normal enteric bacteria. Muc2 is the major structural component of the protective colonic mucus. Our aim was to determine whether primary or induced aberrations in Muc2 synthesis occur in GF IL-10 mice that develop colit...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200411000-00016
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:The early molecular changes preceding the onset of mucosal inflammation in colitis and their temporal relationship with gut permeability remain poorly defined. This study investigated functional and transcriptomic changes in mdr1a(-/-) mice lacking the intestinal transporter P-glycoprotein, which develop col...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20375
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:The cumulative incidence of colectomy and the impact of 5-aminosalicylates (5-ASA), azathioprine, and antitumor necrosis factor (TNF) treatment on the long-term need for surgery are unknown in ulcerative colitis (UC) in the era of biologics. METHODS:This was an observational study of a referral center cohor...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21932
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel disease (IBD) is proposed to result from a dysregulated mucosal immune response to the colonic flora in genetically susceptible individuals. Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subclass of the common human commensal, B. fragilis, has been associated with IBD. This stud...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20265
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:Interleukin-13 (IL-13) is a multifunctional cytokine whose net principle action is to diminish inflammatory responses. Dysregulation of IL-13 production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in IBD pathogenesi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200409000-00014
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. METHODS:In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/ibd.21193
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:Iron is an important nutrient for both the host and colonizing bacteria. Oral iron supplementation may impact the composition of the microbiota and can be particularly damaging to patients suffering from inflammatory bowel disease (IBD). However, patients with IBD may require iron supplementation to treat th...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001089
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel disease (IBD) is a multifactorial disorder, with the innate and adaptive immune cells contributing to disease initiation and progression. However, the intricate cross-talk between immune cell lineages remains incompletely understood. The role of CD8+ T cells in IBD pathogenesis has been un...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz191
更新日期:2020-01-06 00:00:00