Genomes and Genes
Summary: A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.
- Fu Y, Chatur N, Cheong Lee C, Salh B. Hypovitaminosis D in adults with inflammatory bowel disease: potential role of ethnicity. Dig Dis Sci. 2012;57:2144-8 pubmed publisher..We suggest that vitamin D supplementation should be considered in all adult IBD patients. ..
- Sewell G, Hannun Y, Han X, Koster G, Bielawski J, Goss V, et al. Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition. Int J Biochem Cell Biol. 2012;44:1839-46 pubmed publisher..Shotgun lipidomics analysis of macroscopically non-inflamed ileal biopsies showed a significant decrease in this same lipid species with overall preservation of sphingolipid, phospholipid and cholesterol composition...
- Glas J, Wagner J, Seiderer J, Olszak T, Wetzke M, Beigel F, et al. PTPN2 gene variants are associated with susceptibility to both Crohn's disease and ulcerative colitis supporting a common genetic disease background. PLoS ONE. 2012;7:e33682 pubmed publisher..Given recent evidence that PTPN2 regulates autophagosome formation in intestinal epithelial cells, the potential link between PTPN2 and ATG16L1 should be further investigated. ..
- Lippert C, Listgarten J, Davidson R, Baxter S, Poon H, Poong H, et al. An exhaustive epistatic SNP association analysis on expanded Wellcome Trust data. Sci Rep. 2013;3:1099 pubmed publisher..Our work suggests that carefully combining data from large repositories could reveal many new biological insights through increased power. As a community resource, all results have been made available through an interactive web server. ..
- Dinu I, Mahasirimongkol S, Liu Q, Yanai H, Sharaf Eldin N, Kreiter E, et al. SNP-SNP interactions discovered by logic regression explain Crohn's disease genetics. PLoS ONE. 2012;7:e43035 pubmed publisher..R codes, data examples, and a ReadMe file are available for download from our website: http://www.ualberta.ca/~yyasui/homepage.html. ..
- Durães C, Machado J, Portela F, Rodrigues S, Lago P, Cravo M, et al. Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II). Inflamm Bowel Dis. 2013;19:230-9 pubmed publisher..07); the OR for positive response to biologic therapy is 3.66. A multilocus approach using autophagy-related genes provides insight into CD phenotype-genotype associations and genetic markers for predicting therapeutic responses. ..
- Sewell G, Rahman F, Levine A, Jostins L, Smith P, Walker A, et al. Defective tumor necrosis factor release from Crohn's disease macrophages in response to Toll-like receptor activation: relationship to phenotype and genome-wide association susceptibility loci. Inflamm Bowel Dis. 2012;18:2120-7 pubmed publisher..Abnormal TNF secretion is evident downstream of multiple TLRs, affects all disease phenotypes, and is unrelated to 34 polymorphisms associated with CD by GWAS. ..
- Hueber W, Sands B, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins P, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693-700 pubmed publisher..00035 Bonferroni-corrected). Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo. This trial was registered at ClinicalTrial.gov with the number NCT01009281. ..
- Hovde Ø, Moum B. Epidemiology and clinical course of Crohn's disease: results from observational studies. World J Gastroenterol. 2012;18:1723-31 pubmed publisher..To date, the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor (TNF)-?-blockers. Azathioprine/methotrexate and TNF-?-blockers are effective in maintaining remission. ..
- Cooke J, Zhang H, Greger L, Silva A, Massey D, Dawson C, et al. Mucosal genome-wide methylation changes in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18:2128-37 pubmed publisher..Consistent differences in DNA methylation between IBD cases and controls at regulatory sites within these genes suggest that their altered transcription contributes to IBD pathogenesis. ..
- Werner L, Paclik D, Fritz C, Reinhold D, Roggenbuck D, Sturm A. Identification of pancreatic glycoprotein 2 as an endogenous immunomodulator of innate and adaptive immune responses. J Immunol. 2012;189:2774-83 pubmed publisherPancreatic autoantibodies are Crohn disease-specific serologic markers. The function and immunological role of their recently identified autoantigen, glycoprotein 2 (GP2), are unknown...
- Mayberry J, Lobo A, Ford A, Thomas A. NICE clinical guideline (CG152): the management of Crohn's disease in adults, children and young people. Aliment Pharmacol Ther. 2013;37:195-203 pubmed publisher..Algorithms have been produced together with a NICE pathway and implementation tools. These are the first evidence-based clinical and cost-effectiveness guidelines for Crohn's disease in the United Kingdom. ..
- Fransen K, Mitrovič M, van Diemen C, Thelma B, Sood A, Franke A, et al. Limited evidence for parent-of-origin effects in inflammatory bowel disease associated loci. PLoS ONE. 2012;7:e45287 pubmed publisher..We present limited evidence for POO effects for the tested IBD loci. POO effects explain part of the hidden heritability for complex genetic diseases but need to be investigated further. ..
- Chan S, Luben R, Olsen A, Tjonneland A, Kaaks R, Teucher B, et al. Body mass index and the risk for Crohn's disease and ulcerative colitis: data from a European Prospective Cohort Study (The IBD in EPIC Study). Am J Gastroenterol. 2013;108:575-82 pubmed publisher..11). Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD. ..
- Wang M, Okazaki T, Kugathasan S, Cho J, Isaacs K, Lewis J, et al. Contribution of higher risk genes and European admixture to Crohn's disease in African Americans. Inflamm Bowel Dis. 2012;18:2277-87 pubmed publisher..Established NOD2, SLC22A4-A5, and ATG16L1 variants show increased CD risk, with IBD5 recessive. Although CD is more common in whites, European admixture is similar among AA cases and controls. ..
- Bakker S, Dik V, Witte B, Lips P, Roos J, van Bodegraven A. Increase in bone mineral density in strictly treated Crohn's disease patients with concomitant calcium and vitamin D supplementation. J Crohns Colitis. 2013;7:377-84 pubmed publisher..Follow-up of BMD in CD patients showed a contraintuitive small increase of BMD at lumbar spine and total hip in CD patients only using supplemental vitamin D and calcium next to strict treatment of CD. ..
- Katsanos K, Voulgari P, Tsianos E. Inflammatory bowel disease and lupus: a systematic review of the literature. J Crohns Colitis. 2012;6:735-42 pubmed publisher..However, the role TNFalpha plays in humans with SLE and IBD is controversial and data on the likely effects of blocking TNFalpha on anti-DNA autoantibody production is always of interest. ..
- Ventham N, Kennedy N, Nimmo E, Satsangi J. Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics. Gastroenterology. 2013;145:293-308 pubmed publisher..We review recent progress in identification of genetic factors associated with IBD and discuss epigenetic mechanisms that could affect development and progression of IBD. ..
- Kulkarni S, Qi Y, O hUigin C, Pereyra F, Ramsuran V, McLaren P, et al. Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease. Proc Natl Acad Sci U S A. 2013;110:20705-10 pubmed publisher..levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3'UTR...
- Azuara D, Rodriguez Moranta F, De Oca J, Sanjuan X, Guardiola J, Lobatón T, et al. Novel methylation panel for the early detection of neoplasia in high-risk ulcerative colitis and Crohn's colitis patients. Inflamm Bowel Dis. 2013;19:165-73 pubmed publisher..006). Analysis of a panel of methylation markers may help in the early identification of colorectal dysplasia or cancer in high-risk IBD patients. ..
- RANDALL C, Vizuete J, Wendorf G, Ayyar B, Constantine G. Current and emerging strategies in the management of Crohn's disease. Best Pract Res Clin Gastroenterol. 2012;26:601-10 pubmed publisher..g. salicylates, immunomodulators) have been studied for many decades, newer approaches including anti-TNF monoclonal antibodies (biologics), and gut selective agents are changing the paradigm we use to treat this debilitating condition. ..
- Papa E, Docktor M, Smillie C, Weber S, Preheim S, Gevers D, et al. Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease. PLoS ONE. 2012;7:e39242 pubmed publisher..Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients. ..
- Zorzi F, Monteleone I, Sarra M, Calabrese E, Marafini I, Cretella M, et al. Distinct profiles of effector cytokines mark the different phases of Crohn's disease. PLoS ONE. 2013;8:e54562 pubmed publisher..Distinct mucosal profiles of cytokines are produced during the different phases of CD. A better understanding of the cytokines temporally regulated in CD tissue could help optimize therapeutic interventions in CD. ..
- Kovács M, Lakatos P, Papp M, Jacobsen S, Nemes E, Polgár M, et al. Pancreatic autoantibodies and autoantibodies against goblet cells in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2012;55:429-35 pubmed..Moreover, association with NOD2/CARD15 and disease phenotype was determined...
- Maurano M, Humbert R, Rynes E, Thurman R, Haugen E, Wang H, et al. Systematic localization of common disease-associated variation in regulatory DNA. Science. 2012;337:1190-5 pubmed publisher..Our results suggest pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders...
- Kenny E, Pe er I, Karban A, Ozelius L, Mitchell A, Ng S, et al. A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci. PLoS Genet. 2012;8:e1002559 pubmed publisher..2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim. ..
- Abraham G, Kowalczyk A, Zobel J, Inouye M. Performance and robustness of penalized and unpenalized methods for genetic prediction of complex human disease. Genet Epidemiol. 2013;37:184-95 pubmed publisher..This has fundamental ramifications for the selection and future development of methods to genetically predict human disease. ..
- Fasci Spurio F, Aratari A, Margagnoni G, Doddato M, Papi C. Early treatment in Crohn's disease: do we have enough evidence to reverse the therapeutic pyramid?. J Gastrointestin Liver Dis. 2012;21:67-73 pubmed..The conclusion is that an indiscriminate top-down approach does not seem to be appropriate for all patients with moderate to severe Crohn's disease. ..
- McCole D. Regulation of epithelial barrier function by the inflammatory bowel disease candidate gene, PTPN2. Ann N Y Acad Sci. 2012;1257:108-14 pubmed publisher..These data identify an important functional role for PTPN2 as a protector of the intestinal epithelial barrier and provide clues as to how PTPN2 mutations may contribute to the pathophysiology of CD. ..
- Beaugerie L, Sokol H. Clinical, serological and genetic predictors of inflammatory bowel disease course. World J Gastroenterol. 2012;18:3806-13 pubmed publisher..At the moment, no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified. ..
- Cleynen I, Gonzalez J, Figueroa C, Franke A, McGovern D, Bortlik M, et al. Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project. Gut. 2013;62:1556-65 pubmed publisher..This large multicentre cohort study has found several genetic and clinical factors influencing the clinical course of CD. NOD2 and early immunomodulator use are the clinically most meaningful predictors for its clinical course. ..
- Ellinghaus D, Ellinghaus E, Nair R, Stuart P, Esko T, Metspalu A, et al. Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. Am J Hum Genet. 2012;90:636-47 pubmed publisherPsoriasis (PS) and Crohn disease (CD) have been shown to be epidemiologically, pathologically, and therapeutically connected, but little is known about their shared genetic causes...
- Schreiber S, Reinisch W, Colombel J, Sandborn W, Hommes D, Robinson A, et al. Subgroup analysis of the placebo-controlled CHARM trial: increased remission rates through 3 years for adalimumab-treated patients with early Crohn's disease. J Crohns Colitis. 2013;7:213-21 pubmed publisher..Clinical remission rates through 3 years of treatment were highest in the shortest disease duration subgroup in adalimumab-treated patients, with a trend to fewer side effects. ..
- Schulthess J, Meresse B, Ramiro Puig E, Montcuquet N, Darche S, Begue B, et al. Interleukin-15-dependent NKp46+ innate lymphoid cells control intestinal inflammation by recruiting inflammatory monocytes. Immunity. 2012;37:108-21 pubmed publisher..Preliminary evidence suggests that this pathway might operate in Crohn's disease. ..
- Ellinghaus D, Zhang H, Zeissig S, Lipinski S, Till A, Jiang T, et al. Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies. Gastroenterology. 2013;145:339-47 pubmed publisher..NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD. ..
- Chang J, Ocvirk S, Berger E, Kisling S, Binder U, Skerra A, et al. Endoplasmic reticulum stress response promotes cytotoxic phenotype of CD8??+ intraepithelial lymphocytes in a mouse model for Crohn's disease-like ileitis. J Immunol. 2012;189:1510-20 pubmed publisher..In conclusion, ER stress-associated UPR mechanisms promote the development and maintenance of the pathogenic cytotoxic CD8??(+) IEL phenotype in the mouse model of Crohn's disease-like ileitis. ..
- Alhagamhmad M, Day A, Lemberg D, Leach S. An update of the role of nutritional therapy in the management of Crohn's disease. J Gastroenterol. 2012;47:872-82 pubmed publisher..This review discusses the role of exclusive enteral nutrition as a therapeutic option for the treatment of Crohn's disease, as well as the latest findings into its mechanisms of action. ..
- Ren J, Wu X, Liao N, Wang G, Fan C, Liu S, et al. Prevention of postoperative recurrence of Crohn's disease: Tripterygium wilfordii polyglycoside versus mesalazine. J Int Med Res. 2013;41:176-87 pubmed publisher..To explore effectiveness and safety of polyglycosides of Tripterygium wilfordii (GTW) and mesalazine (5-aminosalicylic acid [5-ASA]) in preventing postoperative clinical and endoscopic recurrence of Crohn's disease...
- Sherlock M, Walters T, Tabbers M, Frost K, Zachos M, Muise A, et al. Infliximab-induced psoriasis and psoriasiform skin lesions in pediatric Crohn disease and a potential association with IL-23 receptor polymorphisms. J Pediatr Gastroenterol Nutr. 2013;56:512-8 pubmed publisherInfliximab (IFX), an established therapy for pediatric Crohn disease (CD), is also efficacious in treating psoriasis, a skin disorder, in which tumor necrosis factor-? is implicated pathogenically...
- Elding H, Lau W, Swallow D, Maniatis N. Refinement in localization and identification of gene regions associated with Crohn disease. Am J Hum Genet. 2013;92:107-13 pubmed publisherThe risk of Crohn disease (CD) has a large genetic component. A recent meta-analysis of 6 genome-wide association studies reported 71 chromosomal intervals but does not account for all of the known genetic contribution...
- Kellermayer R, Mir S, Nagy Szakál D, Cox S, Dowd S, Kaplan J, et al. Microbiota separation and C-reactive protein elevation in treatment-naïve pediatric granulomatous Crohn disease. J Pediatr Gastroenterol Nutr. 2012;55:243-50 pubmed publisher..bowel diseases (IBDs), the presence of noncaseating mucosal granuloma is sufficient for diagnosing Crohn disease (CD) and may represent a specific immune response or microbial-host interaction...
- Xue L, Xu K, Zhang W, Wang Q, Wu J, Wang X. Associations between vitamin D receptor polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis. Inflamm Bowel Dis. 2013;19:54-60 pubmed publisher..For males, the TaqI tt genotype is associated with susceptibilities to both UC and CD. Our study explored the genetic risk prediction in UC and CD, and may provide valuable insights into IBD therapy. ..
- Moon C, Shin D, Kim S, Son N, Park A, Park B, et al. Associations between genetic variants in the IRGM gene and inflammatory bowel diseases in the Korean population. Inflamm Bowel Dis. 2013;19:106-14 pubmed publisher..However, there was no significant association between the four SNPs and UC susceptibility. This is the first study to identify SNP rs10065172 and rs72553867 in IRGM as principal CD susceptibility loci in an Asian population. ..
- Camus M, Seksik P, Bourrier A, Nion Larmurier I, Sokol H, Baumer P, et al. Long-term outcome of patients with Crohn's disease who respond to azathioprine. Clin Gastroenterol Hepatol. 2013;11:389-94 pubmed publisher..These benefits, however, could be offset by an increased risk of malignancies. ..
- De Greef E, Vandenplas Y, Hauser B, Devreker T, Veereman Wauters G. Probiotics and IBD. Acta Gastroenterol Belg. 2013;76:15-9 pubmed..Results have so far been disappointing for Crohn's disease but encouraging for ulcerative colitis. An overview of studies using probiotics in adults or children and a perspective on specific pediatric issues is provided in this review...
- Xiang Z, Chen Y, Ye Y, Ma K, Chen S, Zheng L, et al. Helicobacter pylori and Crohn's disease: a retrospective single-center study from China. World J Gastroenterol. 2013;19:4576-81 pubmed publisher..To investigate the association between Helicobacter pylori (H. pylori) infection and the prevalence of Crohn's disease (CD)...
- Gersemann M, Becker S, Nuding S, Antoni L, Ott G, Fritz P, et al. Olfactomedin-4 is a glycoprotein secreted into mucus in active IBD. J Crohns Colitis. 2012;6:425-34 pubmed publisher..Olfactomedin-4 (OLFM4) is a glycoprotein characteristic of intestinal stem cells and apparently involved in mucosal defense of the stomach and colon. Here we studied its expression, regulation and function in IBD...