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Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.
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PMID:Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease. 1884 Apr 43

The volume of research undertaken on the genetic susceptibility of inflammatory bowel disease (IBD) has been tremendous. Genome-wide linkage studies pointed towards more than 10 chromosomal regions and fine-mapping of these regions led to the identification of a number of genes, including CARD15 (NOD2), DLG5, OCTN1 and 2, TLR4 and CARD4 (NOD1). With the recent completion of the human genome project, whole genome association studies (WGAS) have now become possible and have identified additional genes (IL23R, IRGM, PTGER4, ATG16L1) for Crohn's disease and ulcerative colitis, that have subsequently been replicated. At present, the CARD15 gene is still the most understood susceptibility gene, explaining around 20% of the genetic predisposition to Crohn's disease. Prediction of disease phenotype and response to the main therapies has for many years been a dream for physicians treating IBD patients. Only now, we start to accumulate some evidence proving that genetic factors indeed influence both the clinical course of IBD patients and their likelihood of responding to certain therapies. In the coming years, we expect an exponential increase in the efforts devoted to research in this area. The optimal prediction of both disease behaviour and response to therapy might result from complex combinations of clinical, biochemical, serological and genetic factors.
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PMID:The role of genetics in inflammatory bowel disease. 1847 63

A patient from the University of North Carolina Hospitals is presented who developed Crohn's disease of the ileal J-pouch following restorative proctocolectomy for ulcerative colitis. Inflammation of the ileal pouch in human inflammatory bowel disease (IBD) represents the best clinical example of the importance of host-enteric microbial interactions, and this case highlights rapid advances in our understanding of the role of the enteric microbiota in the immunopathogenesis of IBD, impacting on clinical care. Successful management of this patient necessitated accurate diagnosis as there are several inflammatory and non-inflammatory conditions of the pouch that present with similar symptoms. Diagnostic measures included serologic assays of response to microbial antigens, including ASCA, anti-OmpC, anti-Cbir1, and pANCA with DNAse sensitivity. Although the serologic detection of selective loss of tolerance to microbial antigens defines clinically important subgroups of inflammatory bowel disease patients, the clinical value of these serodiagnostic tests is a matter of debate. Genome wide screens have also identified NOD2/CARD15, IL23 receptor, and ATG16L1 variants as important in IBD susceptibility and pathogenesis. These genetic associations have also provided new insights into the importance of interaction between the host and microbes in the pathogenesis of IBD, but the precise mechanisms by which these gene variants contribute to disease development remain to be determined. Genetic associations and serological markers will ultimately be used to define important clinical subgroups of disease, predict natural history, and ultimately identify patient populations for early therapeutic intervention.
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PMID:Abnormal mucosal immune response to altered bacterial flora following restorative proctocolectomy in patients with ulcerative colitis: serologic measures, immunogenetics, and clinical correlations. 2123 20

Genome-wide association studies efficiently and powerfully assay common genetic variation. The application of these studies to Crohn's disease has provided insight into the immunopathogenesis of this disease, implicating a role for genes of the innate and adaptive immune systems. In this Review, I discuss our current understanding of the genetics and immunopathogenesis of Crohn's disease and ulcerative colitis. Crohn's disease, but not ulcerative colitis, is associated with genetic variation in NOD2 and an autophagy gene, ATG16L1, both of which affect the intracellular processing of bacterial components. By contrast, variation in the gene encoding the interleukin-23 (IL-23) receptor subunit, as well as in the IL12B, STAT3 and NKX2-3 gene regions, is associated with both Crohn's disease and ulcerative colitis. Comparative analyses of gene associations between these two inflammatory bowel diseases reveal common and unique mechanisms of their immunopathogenesis.
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PMID:The genetics and immunopathogenesis of inflammatory bowel disease. 1850 Feb 30

Inflammatory bowel disease is a complex multifactorial disease with a strong genetic component. Recent studies have identified innate immunity (NOD2), autophagy (ATG16L1) and Th17 pathway (IL23R) genes in the pathogenesis of Crohn's disease. The pathogenesis of ulcerative colitis (UC) is less clear; however, there is growing evidence that proteins involved in the apical junction complex are involved in UC. Here we review the up-to-date studies on the genetic basis for IBD and explore the newly described UC-associated apical junction complex pointing to a primary defect in barrier defense. We will focus on the PTPRS (encoding PTPsigma) gene and discuss its and other apical junction complex proteins' role in the pathogenesis of UC.
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PMID:Apical junction complex proteins and ulcerative colitis: a focus on the PTPRS gene. 1859 28

Crohn's disease and ulcerative colitis are chronic inflammatory disorders caused by a disruptive interaction between the immune system and gut luminal factors. Although the exact aetiology of IBD remains unclear, accumulating data, including genome-wide association studies (GWAS), have advanced our understanding of the immunopathogenesis. This review highlights the role in gut homeostasis and IBD pathogenesis. It focuses on past and recent advances in our understanding of IBD, including genetics and immunobiology. Recently published GWAS have confirmed earlier findings related to the NOD2 gene and the IBD5 locus. In addition, over 30 novel loci have been identified. Several promising associations between Crohn's disease and gene variants have been identified and replicated, the two most widely replicated being variants in the IL23R and ATG16L1 genes. These findings highlight and further support the importance of the immune system and its interactions with the intestinal flora in the pathogenesis of inflammatory bowel disease.
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PMID:Update on genetics in inflammatory disease. 1941 49

The aim of this study was to determine the role of the ATG16L1 (rs2241880) and IRGM (rs13361189 and rs4958847) genes polymorphism in Crohn's disease (CD) and ulcerative colitis (UC). Our study included 557 CD and 425 UC patients and 672 ethnically matched Spanish controls and a meta-analysis with the data published to date. The polymorphisms were genotyped using predesigned TaqMan single nucleotide polymorphism genotyping assays. There was a statistically significant difference in the distribution of the ATG16L1 rs2241880 G allele between CD patients and controls in the Spanish population: P=6.5 x 10(-9), odds ratio (OR)=1.62. Although no differences were observed between UC patients and controls in the Spanish cohort, a meta-analysis demonstrated that the ATG16L1 G allele increase significantly risk for UC (P=0.0003, pooled OR=1.08). In addition, our meta-analysis data showed that IRGM rs13361189 and rs4958847 polymorphisms were associated with CD (rs13361189 C allele P=1.07 x 10(-19), pooled OR=1.34; rs4958847 A allele P=2.78 x 10(-17), pooled OR=1.31) and UC (rs13361189 P=0.0069, pooled OR=1.16; rs4958847 P=0.014, pooled OR=1.13). In conclusion, our results confirm the ATG16L1 rs2241880 and IRGM rs13361189 and rs4958847 polymorphisms as important markers for CD susceptibility and indicate that these variants are also associated with UC.
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PMID:Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach. 1949 42

Epidemiological data, detailed molecular studies and recent genome-wide association studies strongly suggest that ulcerative colitis (UC) and Crohn's disease (CD) are related polygenic diseases that share some susceptibility loci, but differ at others. To date, there are more than 50 confirmed inflammatory bowel disease genes/loci, a number that is widely anticipated to at least double in the next 2 years. Germline variation in IL23R, IL12B, JAK2 and STAT3 is associated with inflammatory bowel disease susceptibility, consistent with the newly described role for IL23 signaling and Th17 cells in disease pathogenesis. Several genes involved in different aspects of bacterial handling are defective only in CD, including NOD2 and the autophagy genes ATG16L1 and IRGM. IL10 and ECM1 are associated with UC, while inherited variation at the HLA region is related to an inflammatory colonic phenotype. The application of genome-wide association studies to inflammatory bowel disease has been successful in defining the genetic architecture of CD and UC and in delivering genuinely novel and important insights into disease pathogenesis. This has unearthed a plethora of attractive targets for the development of future therapeutics. Insights into the natural history of these complex diseases will follow and may enable appropriate patient selection for early aggressive therapy with the view to modifying the disease course.
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PMID:Genetics of inflammatory bowel disease: implications for disease pathogenesis and natural history. 1981 73

Twin studies and large-scale population studies have confirmed an increased sibling risk for both Crohn's disease (CD) and ulcerative colitis (UC). Unlike single gene disorders, CD and UC are thought to result from a complex interplay of multiple genes and environmental factors. The confirmation of CARD15/NOD2 as a CD susceptibility gene in the late 1990s caused much excitement in the field of complex diseases in general and since then, the rapid rate of progress in molecular genetics, with the advent of large-scale affordable genotyping techniques, has resulted in large collaborations and the identification of over 30 inflammatory bowel disease (IBD)-associated genes. In particular, the importance of the innate immune system has been reaffirmed with the identification of IRGM and ATG16L1 genes in the autophagy pathway as CD susceptibility genes. Disturbance in the adaptive immune system, in particular the IL-23/Th17 axis, has also shown to be of importance for IBD overall. In this era of genome-wide association studies it may be possible to, at last, identify the multiple genes involved in IBD and thus improve our understanding of the genotype-phenotype correlation and improve treatment.
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PMID:The genetic basis of inflammatory bowel disease. 1989 57

The genetic component of Inflammatory Bowel Diseases is among the best known for complex genetic disorders. If the functional candidate gene approach was rarely fruitful in the past, genome-wide scans allowed finding several susceptibility genes for Crohn disease including NOD2, IL23R, ATG16L1, IRGM, TNFSF15, a region close to PTGER4, PTPN2, PTPN22, NKX2-3 and many others. Only one gene, ECM1, has been reported for ulcerative colitis alone. We now need to further explore these new genes before to understand their biological role. However they clearly demonstrate the importance of innate immunity and autophagy for Crohn's disease and of the TH-17 differentiation for ulcerative colitis, Crohn's disease and other inflammatory disorders.
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PMID:Inflammatory Bowel Diseases: the genetic revolution. 2011 35


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