Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Genome-wide association studies have identified PHOX2B, FAM92B, IRGM and NCF4 as candidate susceptibility factors for ileal Crohn's disease (CD). Here we sought to determine whether these genes were also associated with ileal CD in New Zealand Caucasians, as well as with ileocolonic CD, colonic CD and ulcerative colitis (UC). A total of 507 CD patients, 475 UC patients and 576 controls were genotyped for the single nucleotide polymorphisms rs16853571 (PHOX2B), rs4821544 (NCF4), rs13361189 and rs4958847 (IRGM), and rs8050910 (FAM92B). NCF4 and IRGM were significantly associated with ileal CD (P-value(rs4821544)=0.0090, odds ratio (OR)=1.425, 95% confidence interval (CI): 1.092-1.859; P-value(rs13361189)=0.0017, OR=1.942, 95% CI: 1.274-2.959; P-value(rs4958847)=0.0022, OR=1.767, 95% CI: 1.224-2.558), but not with other forms of inflammatory bowel disease (IBD). No association of PHOX2B or FAM92B with IBD was detected. Our study has demonstrated that IRGM and NCF4 are ileal-specific CD susceptibility factors in New Zealand Caucasians.
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PMID:Confirmation of association of IRGM and NCF4 with ileal Crohn's disease in a population-based cohort. 1858 Aug 84

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

Inflammatory bowel disease (IBD) consists of two main disorders, ulcerative colitis and Crohn's disease, that cause chronic, recurrent inflammation of the intestine. An inappropriate immune response to the enteric ecosystem has been postulated to cause IBD. Genomewide association studies provide the information of diverse genetic variations and susceptibilities to patients with IBD. Through the application of these studies, the pathogenesis of IBD may result in part from genetic abnormalities that regulate epithelial barrier function and innate and adaptive immune responses. Crohn's disease shows strong association with CARD15, ATG15L1, and IRGM, which are involved in the innate immunity. In the adaptive immune response, IL23R, MST1, IL12B, and STAT3 polymorphisms are associated with Crohn's disease and ulcerative colitis. Current pharmacologic treatment of IBD, including 5-aminosalycylate, steroids, and immunomodulator therapy, are mainly aimed at suppressing inflammation non-specifically, except biologic therapies such as anti-tumor necrosis factor molecule, which block specific proinflammatory molecules. For nutritional issues in IBD, the mainstay of therapy has been supportive, with particular attention paid to the prevention, recognition, and therapy of nutritional deficiencies, and individual outcomes to specific dietary factors have been controversial. Parenteral nutritional support and exclusionary diets have been investigated and are not the subject of this review. The emerging concepts of nutrition-gene interaction gave birth to unique scientific fields, nutrigenetics and nutrigenomics. These studies provide information about 1) the genetic variability that induces an individual's response to nutrition according to particular states of health and disease and 2) changes in gene expression that develop as a result of nutrition-gene interaction. For IBD, the role of diet in the regulation of the immune response against gut flora is the subject of current intensive evaluation. These approaches may lead clinicians to derive a personalized nutritional prescription based on individual genetic variations and may result in a significant impact on IBD treatment.
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PMID:DNA-driven nutritional therapy of inflammatory bowel disease. 1964 22

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

Inflammatory bowel diseases (IBD) are common inflammatory disorders of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD are high in North America and Europe, affecting as many as one in 500 people. These diseases are associated with high morbidity and mortality. Colorectal cancer risk is also increased in IBD, correlating with inflammation severity and duration. IBD are now recognized as complex multigenetic disorders involving at least 32 different risk loci. In 2007, two different autophagy-related genes, ATG16L1 (autophagy-related gene 16-like 1) and IRGM (immunity-related GTPase M) were shown to be specifically involved in CD susceptibility by three independent genome-wide association studies. Soon afterwards, more than forty studies confirmed the involvement of ATG16L1 and IRGM variants in CD susceptibility and gave new information on the importance of macroautophagy (hereafter referred to as autophagy) in the control of infection, inflammation, immunity and cancer. In this review, we discuss how such findings have undoubtedly changed our understanding of CD pathogenesis. A unifying autophagy model then emerges that may help in understanding the development of CD from bacterial infection, to inflammation and finally cancer. The Pandora's box is now open, releasing a wave of hope for new therapeutic strategies in treating Crohn's disease.
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PMID:Autophagy and Crohn's disease: at the crossroads of infection, inflammation, immunity, and cancer. 2054 Jul 3

Crohn's disease (CD) and ulcerative colitis (UC) have features that suggest bacterial involvement, and all genetic models of inflammatory bowel disease (IBD) require the presence of commensal bacteria. CD is associated with innate immune response genes such as NOD2/CARD15 and the autophagy genes ATG16L1 and IRGM. However, IBD responds to immunosuppression, suggesting that any bacteria involved are not acting as conventional pathogens. Molecular techniques are rapidly advancing our knowledge of the gut microbiota. In CD there is reduced diversity, and notably a reduction in the probiotic Faecalibacterium prausnitzii, the presence of which in the terminal ileum is associated with a reduced risk of recurrence following surgery. There is also a consistent increase in mucosa-associated Escherichia coli with an "adherent and invasive" phenotype, which allows them to replicate inside macrophages and induce granulomas. Speculation that CD could be caused by the Mycobacterium avium subspecies paratuberculosis (MAP) continues. The response to antitumor necrosis factor treatments suggests that, if relevant at all, MAP is not acting as a conventional pathogen. However, there is increased colonization by MAP in CD, and there is evidence that it could have an indirect effect mediated by the suppression of macrophage function. UC relapse is frequently associated with infection by pathogens, but there is less evidence for involvement of a specific bacterial species. Poor barrier integrity followed by an inflammatory reaction to bacterial components, with chronicity maintained by an autoimmune process, seems a plausible pathogenic model. Bacterial theories of pathogenesis are now becoming testable by targeted therapeutic interventions.
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PMID:The role of bacteria in the pathogenesis of inflammatory bowel disease. 2098 Dec 5


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