inflammatory bowel diseases

Types

 Crohn disease

• Crohn colitis

 ulcerative colitis (hemorragic rectoloitis )
 undeterminate colitis

Susceptibility

Genetic association studies have identified 210 risk loci for inflammatory bowel disease, which have revealed fundamental aspects of the molecular biology of the disease, including the roles of autophagy and Th17 cell signaling and development.

A study identified 26 new genome-wide significant loci, three of which contain integrin genes that encode molecules in pathways identified as important therapeutic targets in inflammatory bowel disease.

The associated variants are also correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 , ITGB8 ) and at two previously implicated integrin loci (ITGAL , ICAM1 ).

In all four cases, the stimulus-dependent expression increasing allele also increases disease risk. It identified likely causal missense variants in the primary immune deficiency gene PLCG2 and the negative regulator of inflammation, SLAMF8 .

 Locus IBD1
 Locus IBD2
 Locus IBD3
 Locus IBD4
 Locus IBD5 - 5q31 cytokine gene cluster
 Locus IBD6
 Locus CARD15
 MDR1 Ala893 polymorphism (7q) (14610718)
 variation in DLG5 gene (10q23) encoding a scaffolding protein involved in the maintenance of epithelial integrity (15107852)

Videos

 Colonoscopy of ulcerative colitis

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Open references

 Understanding inflammatory bowel disease via immunogenetics. de Lange KM, Barrett JC. J Autoimmun. 2015 Nov;64:91-100. doi : 10.1016/j.jaut.2015.07.013 PMID: 26257098 (Free)

References

 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. 2016.
doi : 10 1101/058255

 Inflammatory bowel disease biopsies: updated British Society of Gastroenterology reporting guidelines. Roger M Feakins. J Clin Pathol doi : 10 1136/jclinpath-2013-201885

 Ivanov AI, Nusrat A, Parkos CA. The epithelium in inflammatory bowel disease: potential role of endocytosis of junctional proteins in barrier disruption. Novartis Found Symp. 2004;263:115-24; discussion 124-32, 211-8. PMID: 15669638

 Mathew CG, Lewis CM. Genetics of inflammatory bowel disease: progress and prospects. Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R161-8. PMID: 14764625

 Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002 Aug 8;347(6):417-29. PMID: 12167685