Abstract:
BACKGROUND:The pregnane X receptor (PXR/NR1I2) is an important regulator of xenobiotic metabolism and intestinal integrity. However, there are controversial studies on the role of PXR/NR1I2 in inflammatory bowel disease (IBD). We therefore initiated the largest analysis to date on PXR/NR1I2 gene variants in IBD patients. METHODS:Genomic DNA from 2823 individuals of Caucasian origin including 859 patients with Crohn's disease (CD), 464 patients with ulcerative colitis (UC), and 1500 healthy, unrelated controls was analyzed for eight PXR/NR1I2 single nucleotide polymorphisms (SNPs) (rs12721602 (-25564), rs3814055 (-25385), rs1523128 (-24756), rs1523127 (-24381), rs45610735 = p.Gly36Arg (+106), rs6785049 (+7635), rs2276707 (+8055), and rs3814057 (+11156)). In addition, detailed haplotype and genotype-phenotype analyses were performed. RESULTS:The PXR/NR1I2 SNP rs2276707 was weakly associated with UC susceptibility (P = 0.01; odds ratio [OR] 1.27 [1.06-1.52]). None of the other PXR/NR1I2 SNPs were associated with UC or CD susceptibility. However, several rare PXR/NR1I2 haplotypes were highly associated with CD susceptibility. In CD, the strongest disease association was found for a haplotype consisting of the SNPs rs12721602-rs3814055-rs1523128-rs1523127-rs12721607-rs6785049-rs2276707-rs3814057 (omnibus P-value: 6.50 × 10(-15)) which was found in two separate cohorts (cohort I = discovery cohort: CD: n = 492, controls: n = 793; P = 4.51 × 10(-17); Bonferroni corrected: P = 1.27 × 10(-15); cohort II = replication cohort: CD: n = 367, controls: n = 707; P = 7.12 × 10(-4); P(corr) = 1.99 × 10(-2)). CONCLUSIONS:Several PXR/NR1I2 haplotypes contribute to CD susceptibility, suggesting a role for PXR in the IBD pathogenesis of a certain patient subcohort. Given the accumulating evidence for an important role of PXR in intestinal inflammation, further analyses are required to investigate the functional and pharmacogenetic implications of these PXR/NR1I2 gene variants in IBD.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Glas J,Seiderer J,Fischer D,Tengler B,Pfennig S,Wetzke M,Beigel F,Olszak T,Weidinger M,Göke B,Ochsenkühn T,Folwaczny M,Müller-Myhsok B,Diegelmann J,Czamara D,Brand Sdoi
10.1002/ibd.21562subject
Has Abstractpub_date
2011-09-01 00:00:00pages
1917-24issue
9eissn
1078-0998issn
1536-4844journal_volume
17pub_type
杂志文章abstract:Background:Standard outpatient induction dosing of infliximab (IFX) may not be effective in hospitalized ulcerative colitis (UC) patients with higher inflammatory burden and colectomy risk. Our aim was to determine whether initial IFX induction dose affects 30-day colectomy rate and other disease-related outcomes. Met...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izx039
更新日期:2018-02-15 00:00:00
abstract::Induction and maintenance of remission, mucosal healing, the avoidance of surgical intervention, and decreasing the likelihood of cancer developing are the primary therapeutic goals in ulcerative colitis (UC). For the traditional therapies, 5-aminosalicylic acid (including mesalamine), corticosteroids, and thiopurines...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1002/ibd.20797
更新日期:2009-06-01 00:00:00
abstract::Mesalamine has a well-established role in the management of ulcerative colitis. However, its role in the management of Crohn's disease (CD) is less clear. Studies evaluating its therapeutic value in CD have produced both positive and negative results. Meta-analyses have not clarified the situation, possibly because th...
journal_title:Inflammatory bowel diseases
pub_type: 评论,社论
doi:10.1097/01.mib.0000160743.24772.69
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:Activation of cannabinoid (CB)(1) receptors results in attenuation of experimental colitis. Our aim was to examine the role of CB(2) receptors in experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB(2) recept...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20960
更新日期:2009-11-01 00:00:00
abstract:Background:The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) is a challenge. The aim of this study was to investigate a predictive model for differential diagnosis between ITB and CD. Methods:A total of 268 patients who were suspected of having ITB or CD were prospectively recruited be...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izy154
更新日期:2018-10-12 00:00:00
abstract:BACKGROUND:According to the Montreal Classification, upper gastrointestinal tract phenotype L4 is uncommon in Caucasian patients with Crohn's disease (CD) but carries excess risk of recurrence. We studied the clinical course of CD in Chinese patients presenting with the L4 phenotype and factors predicting its occurrenc...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20804
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:Improving granulocyte function may represent an effective therapy for Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in children with CD. METHODS:This was multicenter, open-label study in 6-16-year-old patients with moderate to severely active CD. Patients received either 4 or 6 ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,多中心研究
doi:10.1002/ibd.21204
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND:Recent studies have suggested that the downregulation of pregnane X receptor (PXR) may contribute to the susceptibility and exacerbation of Crohn's disease (CD). Because bile acid malabsorption is one of the features of CD and bile acids are potential activators of PXR, we explored the relationship between b...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0b013e318281f423
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:The goal of this study was to determine the rate of work disability, unemployment, and sick leave in an unselected inflammatory bowel disease (IBD) cohort and to measure the effect of working status and disability on the patient's health-related quality of life (HRQOL). MATERIALS AND METHODS:All eligible pa...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000218762.61217.4a
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Although dysplasia is thought to be the precursor lesion in the development of colitis-associated colorectal cancer (CRC), a significant proportion of patients with ulcerative colitis (UC) and low-grade (LGD) or indefinite (IND) dysplasia remain cancer-free during endoscopic follow-up. There is a need for bi...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21722
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:The incidence of inflammatory bowel disease (IBD) has increased over the past several decades with a corresponding increase in the number of patients on combination immunosuppressive therapy including corticosteroids, anti-metabolites and biologic agents. The exact incidence of pneumocystis jiroveci pneumoni...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
doi:10.1097/MIB.0b013e318281f562
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Previous research suggests a link between childhood adversities and inflammatory bowel disease (IBD); however, study limitations prevent generalization of findings. To address this, the current study uses a Canadian population-based sample to investigate the relationship between 3 childhood adversities and 2...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000551
更新日期:2015-11-01 00:00:00
abstract::Recent reports suggest that unfractionated heparin may be a useful adjunct in the treatment of inflammatory bowel disease (IBD). We report the successful use of subcutaneous unfractionated heparin to treat a moderate-to-severe flare of Crohn's disease during pregnancy, which was refractory to standard therapy. The pat...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/00054725-200205000-00006
更新日期:2002-05-01 00:00:00
abstract:BACKGROUND:Ulcerative colitis (UC) negatively affects health-related quality of life (HRQoL), but population-based and long-term data on this topic are scarce. Our aim was to determine the HRQoL in UC patients after a 10-year disease duration. METHODS:UC patients from a population-based inception cohort met at a presc...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21863
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Fulminant Crohn's colitis complicated by toxic dilatation of the large bowel usually requires surgery, which carries a substantial morbidity and mortality rate. METHODS:We report the case of a female with steroid refractory fulminant Crohn's colitis complicated by toxic megacolon who was successfully treate...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20139
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting, and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to pred...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21639
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Minimally invasive surgery for Crohn's ileocolitis is well established but few data exist regarding laparoscopic techniques for Crohn's colitis. We aimed to describe outcomes associated with minimally invasive surgery for Crohn's colitis, including predictors of conversion to laparotomy and postoperative com...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21265
更新日期:2010-11-01 00:00:00
abstract:BACKGROUND:Many patients with Crohn's disease (CD) are treated with medications, including steroids, immunomodulators, and anti-tumor necrosis factor alpha (anti-TNF-α) agents, at the time of surgery. This study evaluated the effects of these medications on postoperative complications in CD patients. METHODS:This retr...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz010
更新日期:2019-08-20 00:00:00
abstract:BACKGROUND:A subset of patients with ulcerative colitis (UC) will require colectomy within a few years of diagnosis. Thus, our aim was to determine the clinical predictors of early colectomy among patients with UC who are hospitalized with an acute flare. METHODS:Using population-based surveillance (1996-2009), all ad...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000001211
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:A novel family of proton-sensing G protein-coupled receptors, including OGR1, GPR4, and TDAG8, was identified to be important for physiological pH homeostasis and inflammation. Thus, we determined the function of proton-sensing OGR1 in the intestinal mucosa. MTEHODS:OGR1 expression in colonic tissues was in...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/MIB.0000000000000375
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:Adverse drug reactions to azathioprine, the prodrug of 6-mercaptopurine, occur in 15%-38% of patients and the majority are not explained by thiopurine-S-methyltransferase (TPMT) deficiency. Azathioprine is known to induce glutathione depletion and consumption of glutathione is greater in cells with high glut...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20004
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Vedolizumab is a gut-selective biologic that has shown efficacy in ulcerative colitis (UC) and Crohn's disease (CD). We studied the pharmacokinetics, pharmacodynamics, safety, tolerability, and efficacy of a new formulation of vedolizumab produced by an improved manufacturing process. METHODS:UC patients we...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,随机对照试验
doi:10.1002/ibd.21896
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:The era of genome-wide association studies (GWAS) has led to the identification of many inflammatory bowel disease (IBD)-associated single-nucleotide polymorphisms (SNPs) with unknown function. The next step would be to identify the functional consequences of these polymorphisms in order to target them effic...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21043
更新日期:2010-02-01 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:Chronic inflammatory diseases are characterized by massive infiltration of innate and acquired immune cells in inflammatory sites. However, it remains unclear how these cells cooperate in the development of disease. Although bone marrow (BM) is a primary site for hematopoiesis of immune cells except T cells,...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.20531
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND:The consistency of endoscopic and histologic findings in patients with ulcerative colitis (UC) has not been elucidated. Choice of assessment may affect study outcomes. METHODS:Post hoc analyses were performed using data from 2 randomized, controlled multicenter trials: (1) SAG-26, mesalazine granules for in...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1097/01.MIB.0000437044.43961.00
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Many treatment options exist for children with inflammatory bowel disease (IBD), yet the lack of clinical guidelines for management has lead to great variation in care. The purpose of this project was to evaluate current treatment modalities in children from the Northeast US who applied to the 2010 session o...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.22837
更新日期:2012-10-01 00:00:00
abstract:Background:We assessed the comparative efficacy of different dysplasia detection techniques in patients with ulcerative colitis (UC) through a network meta-analysis and rated the quality of evidence using GRADE approach. Methods:Through a systematic literature review of multiple databases through June 30, 2017, we ide...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
doi:10.1093/ibd/izy188
更新日期:2018-11-29 00:00:00
abstract:BACKGROUND:Surgery is the preferred option for patients with symptomatic localized fibrostenotic ileocecal Crohn's disease (CD) but not for those with predominantly active inflammation without obstruction. The benefit of early surgery in patients with a limited nonstricturing ileocecal CD over biologic treatment is sti...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1093/ibd/izz282
更新日期:2020-10-23 00:00:00
abstract::: We evaluated retrospective smoking data reported by 221 patients with ulcerative colitis in 1984 and repeated in an identical questionnaire in 1989. Reported years of smoking initiation or smoking cessation agreed to a high extent; the difference between the two questionnaires was in mean (± SD) -0.1 ± 1.5 (median, ...
journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00