A Genome-Wide Association Study Identifies
            <i>IL23R</i>
            as an Inflammatory Bowel Disease Gene

Duerr, Richard H.; Taylor, Kent D.; Brant, Steven R.; Rioux, John D.; Silverberg, Mark S.; Daly, Mark J.; Steinhart, A. Hillary; Abraham, Clara; Regueiro, Miguel; Griffiths, Anne M.; Dassopoulos, Themistocles; Bitton, Alain; Yang, Huiying; Targan, Stephan R.; Datta, Lisa W.; Kistner, Emily O.; Schumm, L. Philip; Lee, Annette T.; Gregersen, Peter K.; Barmada, M. Michael; Rotter, Jerome I.; Nicolae, Dan L.; Cho, Judy H.

doi:10.1126/science.1135245

Cited by 2,707 publications

(2,180 citation statements)

References 29 publications

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“…1,2 To date, different genetic studies have shown several genes playing a relevant role in these diseases, including NOD2/CARD15, 3 DGL5, 4 SLC22A4 and SLC22A5, 5,6 TNFSF15, 7,8 NOD1/CARD4 7 and IL23R. 9,10 NOD2/CARD15 is likely to be the major genetic factor contributing to CD. This gene encodes a protein directly involved in the innate immune response to microbial antigens.…”

Section: Introductionmentioning

confidence: 99%

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

et al. 2009

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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 ¼ 6.5 Â 10 À9 , odds ratio (OR) ¼ 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 ¼ 0.0003, pooled OR ¼ 1.08). In addition, our meta-analysis data showed that IRGM rs13361189 and rs4958847 polymorphisms were associated with CD (rs13361189 C allele P ¼ 1.07 Â 10 À19 , pooled OR ¼ 1.34; rs4958847 A allele P ¼ 2.78 Â 10 À17 , pooled OR ¼ 1.31) and UC (rs13361189 P ¼ 0.0069, pooled OR ¼ 1.16; rs4958847 P ¼ 0.014, pooled OR ¼ 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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Section: Introductionmentioning

confidence: 99%

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

et al. 2009

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“…An IL‐12‐driven Th1 response may dominate during the early stages of CD, implying that susceptibility to IL‐12‐mediated modulation is strongly dependent on the stage of the disease,16 although activities that have been attributed to IL‐12 in the past may have been mediated by IL‐23 17. Several studies have now demonstrated an important role for Th17 cells in intestinal inflammation 18, 19…”

Section: Discussionmentioning

confidence: 99%

Measurement of IL‐12 (p40, p35), IL‐23p19, and IFN‐γ mRNA in Duodenal Biopsies of Cats with Inflammatory Enteropathy

Waly

Peters

Day

et al. 2013

Veterinary Internal Medicne

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BackgroundDietary hypersensitivity and inflammatory bowel disease (IBD) are important causes of chronic vomiting and diarrhea in cats. IL‐23 has been recently found to be a key factor in the immunopathogenesis of IBD in humans but the involvement in IBD has not been investigated in cats.Hypothesis/ObjectivesExpression of genes encoding Il‐12p35 and p40, IL‐23p19, and IFN‐γ may be up‐regulated in duodenal biopsy specimens taken from cats with histologic evidence of inflammation.Animals and MethodsDuodenal biopsy specimens were collected from control cats (n = 21) and cats with inflammatory enteropathy (n = 13). Routine histopathology, immunohistochemistry (IHC), and qRT‐PCR were used to assess expression of MHC class II and to measure gene transcripts encoding the p35, p40, and p19 subunits of the IL‐12 family of cytokines and IFN‐γ.ResultsThere were significant differences in expression of mRNA encoding IL‐12p35 and IL‐23p19 between healthy cats and cats with inflammatory enteropathy. IL‐12p35 mRNA was lower in the duodenal mucosa of cats with inflammatory enteropathy compared with the mucosa of healthy cats (P = .001). In contrast, IL‐23p19 mRNA expression was higher in duodenal biopsy specimens from cats with inflammatory enteropathy than in those from healthy controls (P = .001). There was no difference in expression of IL‐12p40 and IFN‐γ mRNA (P > .05). The majority of cats with inflammatory enteropathy had histologic evidence of moderate to severe colitis (score 2).Conclusions and Clinical ImportanceThe results of this preliminary study suggest that IL‐23 plays a role in the pathogenesis of feline inflammatory enteropathy.

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“…Chez l'homme, une étude d'association pangénomique a en effet identifié le gène il23r (IL-23 receptor), essentiellement exprimé par les lymphocytes Th17 et les ILC3, comme un gène de prédispo-sition aux maladies inflammatoires chroniques de l'intestin [51]. Chez la souris, les ILC3 ont été impliquées dans le développement de colites induites par Helicobacter hepaticus via leur capacité à produire de l'IL-17 et de l'IFN- [23].…”

Section: Les Ilc3unclassified

Les cellules lymphoïdes innées

et al. 2017

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A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene

Abstract: The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study.

Cited by 2,707 publications

References 29 publications

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

Measurement of IL‐12 (p40, p35), IL‐23p19, and IFN‐γ mRNA in Duodenal Biopsies of Cats with Inflammatory Enteropathy

Les cellules lymphoïdes innées

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