IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v411y2001i6837d10.1038_35079114.html
   My bibliography  Save this article

A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease

Author

Listed:
  • Yasunori Ogura

    (The University of Michigan Medical School)

  • Denise K. Bonen

    (The Martin Boyer Laboratories, Gastroenterology Section, The University of Chicago Hospitals)

  • Naohiro Inohara

    (The University of Michigan Medical School)

  • Dan L. Nicolae

    (and)

  • Felicia F. Chen

    (The University of Michigan Medical School)

  • Richard Ramos

    (The Martin Boyer Laboratories, Gastroenterology Section, The University of Chicago Hospitals)

  • Heidi Britton

    (The Martin Boyer Laboratories, Gastroenterology Section, The University of Chicago Hospitals)

  • Thomas Moran

    (The Martin Boyer Laboratories, Gastroenterology Section, The University of Chicago Hospitals)

  • Reda Karaliuskas

    (The Martin Boyer Laboratories, Gastroenterology Section, The University of Chicago Hospitals)

  • Richard H. Duerr

    (University of Pittsburgh)

  • Jean-Paul Achkar

    (The Cleveland Clinic Foundation)

  • Steven R. Brant

    (The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, The Johns Hopkins University School of Medicine)

  • Theodore M. Bayless

    (The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, The Johns Hopkins University School of Medicine)

  • Barbara S. Kirschner

    (University of Chicago)

  • Stephen B. Hanauer

    (The Martin Boyer Laboratories, Gastroenterology Section, The University of Chicago Hospitals)

  • Gabriel Nuñez

    (The University of Michigan Medical School)

  • Judy H. Cho

    (The Martin Boyer Laboratories, Gastroenterology Section, The University of Chicago Hospitals)

Abstract

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies1,2,3,4,5,6, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-κB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.

Suggested Citation

  • Yasunori Ogura & Denise K. Bonen & Naohiro Inohara & Dan L. Nicolae & Felicia F. Chen & Richard Ramos & Heidi Britton & Thomas Moran & Reda Karaliuskas & Richard H. Duerr & Jean-Paul Achkar & Steven R, 2001. "A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease," Nature, Nature, vol. 411(6837), pages 603-606, May.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6837:d:10.1038_35079114
    DOI: 10.1038/35079114
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35079114
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35079114?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Chao Lu & Jun Yang & Weilai Yu & Dejian Li & Zun Xiang & Yiming Lin & Chaohui Yu, 2015. "Association between 25(OH)D Level, Ultraviolet Exposure, Geographical Location, and Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-16, July.
    2. Yogesh Dahiya & Rajeev Kumar Pandey & Ajit Sodhi, 2011. "Nod2 Downregulates TLR2/1 Mediated IL1β Gene Expression in Mouse Peritoneal Macrophages," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-11, November.
    3. Isabelle Cleynen & Peter Jüni & Geertruida E Bekkering & Eveline Nüesch & Camila T Mendes & Stefanie Schmied & Stefan Wyder & Eliane Kellen & Peter M Villiger & Paul Rutgeerts & Séverine Vermeire & Da, 2011. "Genetic Evidence Supporting the Association of Protease and Protease Inhibitor Genes with Inflammatory Bowel Disease: A Systematic Review," PLOS ONE, Public Library of Science, vol. 6(9), pages 1-13, September.
    4. Benjamin Lehne & Cathryn M Lewis & Thomas Schlitt, 2011. "From SNPs to Genes: Disease Association at the Gene Level," PLOS ONE, Public Library of Science, vol. 6(6), pages 1-10, June.
    5. Jingwei Liu & Caiyun He & Qian Xu & Chengzhong Xing & Yuan Yuan, 2014. "NOD2 Polymorphisms Associated with Cancer Risk: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(2), pages 1-10, February.
    6. Nanye Long & Samuel P Dickson & Jessica M Maia & Hee Shin Kim & Qianqian Zhu & Andrew S Allen, 2013. "Leveraging Prior Information to Detect Causal Variants via Multi-Variant Regression," PLOS Computational Biology, Public Library of Science, vol. 9(6), pages 1-11, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:411:y:2001:i:6837:d:10.1038_35079114. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.