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Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1, which offer promise for informed therapeutic development.
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
A meta-analysis of six Crohn's disease genome-wide association studies and a series of in silico analyses highlighted particular genes within these loci implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.
A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene
A highly significant association is found between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23, which prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology.
- M. Silverberg, J. Satsangi, +18 authors B. Warren
- MedicineCanadian journal of gastroenterology = Journal…
- 1 September 2005
The introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.
Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis
It is demonstrated that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium, and these findings suggest thatAutophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.
Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease.
6-MP metabolite levels and TPMT genotyping may assist clinicians in optimizing therapeutic response to 6-MP and identifying individuals at increased risk for drug-induced toxicity.
A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.
A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.
Natalizumab induction and maintenance therapy for Crohn's disease.
- W. Sandborn, J. Colombel, +12 authors P. Rutgeerts
- MedicineThe New England journal of medicine
- 3 November 2005
Induction therapy with natalizumab for Crohn's disease resulted in small, nonsignificant improvements in response and remission rates, which will need to be weighed against the risk of serious adverse events.
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47
A meta-analysis of six ulcerative colitis genome-wide association study datasets found many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1.