Genetic Variation in Myosin IXB Is Associated With Ulcerative Colitis

Bodegraven, Adriaan A. van; Curley, Christine R.; Hunt, Karen A.; Monsuur, Alienke J.; Linskens, Ronald K.; Onnie, Clive M.; Crusius, J. Bart A.; Annese, Vito; Latiano, Anna; Silverberg, Mark S.; Bitton, Alain; Fisher, Sheila; Steinhart, A.H.; Forbes, Alastair; Sanderson, Jeremy; Prescott, Natalie J.; Strachan, David P.; Playford, Raymond J.; Mathew, Christopher G.; Wijmenga, Cisca; Daly, Mark J.; Rioux, John D.; Heel, David A. van

doi:10.1053/j.gastro.2006.09.011

Cited by 97 publications

(108 citation statements)

References 28 publications

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“…This cohort has previously been used and characterized in several association reports from our group (28)(29)(30), and additional cohort information can be found in Supplemental Table 1. The diagnosis of IBD required (a) one or more symptoms of diarrhea, rectal bleeding, abdominal pain, fever, or complicated perianal disease, (b) occurrence of symptoms on two or more occasions separated by at least 8 weeks or ongoing symptoms of at least 6 weeks duration, and (c) objective evidence of inflammation from radiologic, endoscopic, and histologic evaluation.…”

Section: Subject Ascertainment and Diagnostic Classificationmentioning

confidence: 99%

Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis

Goyette

Lefèbvre

et al. 2008

Mucosal Immunology

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Association mapping and candidate gene studies within IBD linkage regions, as well as genomewide association studies in CD have led to the discovery of multiple risk genes, but these only Corresponding author: John D. Rioux, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada, H1T 1C8, rioux@inflammgen.org. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript explain a fraction of the genetic susceptibility observed in IBD. We have thus been pursuing a region on chromosome 3p21-22 showing linkage to CD and UC using a gene-centric association mapping approach. We identified twelve functional candidate genes by searching for literature cocitations with relevant keywords and for gene expression patterns consistent with immune/ intestinal function. We then performed an association study composed of a screening phase, where tagging SNPs were evaluated in 1020 IBD patients, and an independent replication phase in 745 IBD patients. These analyses identified and replicated significant association to IBD for four SNPs within a 1.2 Mb LD region. We then identified a non-synonymous coding variant (rs3197999, R689C) in the macrophage stimulating 1 (MST1) gene (p-value 3.62×10−6) that accounts for the association signal, and shows association to both CD and UC. MST1 encodes MSP, a protein regulating the innate immune responses to bacterial ligands. R689C is predicted to interfere with MSP binding to its receptor, suggesting a role for this gene in the pathogenesis of IBD.

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Section: Subject Ascertainment and Diagnostic Classificationmentioning

confidence: 99%

Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis

Goyette

Lefèbvre

et al. 2008

Mucosal Immunology

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“…Finally, studies of candidate genes that are not located within IBD linkage regions have revealed weak associations between UC and a variable number of tandem repeats polymorphism in the IL1RN gene [106] and between IBD and the TLR4 gene [107][108][109][110][111][112][113] . In a large case-control study, association was observed in UC and CD for Ala1011Ser within the Myo Ⅸb (MYO9B) gene [114] that had been previously been implicated in celiac disease [115] . If replicated, this would indicate shared susceptibility pathways between multiple types of intestinal inflammation.…”

Section: Hla Associationsmentioning

confidence: 99%

Inflammatory bowel disease: Genetic and epidemiologic considerations

Cho

2008

WJG

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Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn's disease. These studies have newly-established the importance of the interleukin 23 and autophagy pathways in disease pathogenesis. Future challenges include: (1) the establishment of precisely causal alleles, (2) definition of altered functional outcomes of associated and causal alleles and (3) integration of genetic findings with environmental factors.

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“…Recent insights from the genetics of in ammatory bowel disease susceptibility have raised this possibility. 28 Targeted association studies have led to the identi cation of the NOD2 gene for Crohn ' s disease, MYO9B for ulcerative colitis, and MST1 gene for both Crohn ' s and colitis. 28 -31 Genome-wide association studies have identi ed ATG16L1 and IRGM genes as genetic risk factors for Crohn ' s, evidence that autophagy plays an important role in gut homeostasis.…”

Section: The Epithelium As a Bystander Participant And Organizer Ofmentioning

confidence: 99%

Recent insights into the integration of the intestinal epithelium within the mucosal environment in health and disease

Blumberg

Nusrat

et al. 2008

Mucosal Immunology

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Genetic Variation in Myosin IXB Is Associated With Ulcerative Colitis

Cited by 97 publications

References 28 publications

Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis

Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis

Inflammatory bowel disease: Genetic and epidemiologic considerations

Recent insights into the integration of the intestinal epithelium within the mucosal environment in health and disease

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