Skip to main content
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 2004 Jul;89(7):598–603. doi: 10.1136/adc.2003.041046

Unravelling the complex genetics of inflammatory bowel disease

R Russell 1, D Wilson 1, J Satsangi 1
PMCID: PMC1720000  PMID: 15210486

Full Text

The Full Text of this article is available as a PDF (223.3 KB).

Figure 1.

Figure 1

 The interaction of NOD 2/CARD 15 within the cell. (Reprinted from Bonen DK et al. The genetics of inflammatory bowel disease. Gastroenterology 2003;124(2):530, with permission from the American Gastroenterological Association)

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahmad T., Satsangi J., McGovern D., Bunce M., Jewell D. P. Review article: the genetics of inflammatory bowel disease. Aliment Pharmacol Ther. 2001 Jun;15(6):731–748. doi: 10.1046/j.1365-2036.2001.00981.x. [DOI] [PubMed] [Google Scholar]
  2. Ahmad Tariq, Armuzzi Alessandro, Bunce Mike, Mulcahy-Hawes Kim, Marshall Sara E., Orchard Timothy R., Crawshaw Jonathan, Large Oliver, de Silva Arjuna, Cook Julia T. The molecular classification of the clinical manifestations of Crohn's disease. Gastroenterology. 2002 Apr;122(4):854–866. doi: 10.1053/gast.2002.32413. [DOI] [PubMed] [Google Scholar]
  3. Armitage E., Drummond H. E., Wilson D. C., Ghosh S. Increasing incidence of both juvenile-onset Crohn's disease and ulcerative colitis in Scotland. Eur J Gastroenterol Hepatol. 2001 Dec;13(12):1439–1447. doi: 10.1097/00042737-200112000-00007. [DOI] [PubMed] [Google Scholar]
  4. Bairead Emer, Harmon Dawn L., Curtis Anne M., Kelly Yvette, O'Leary Clare, Gardner Michelle, Leahy Dermot T., Vaughan Pat, Keegan Denise, O'Morain Colm. Association of NOD2 with Crohn's disease in a homogenous Irish population. Eur J Hum Genet. 2003 Mar;11(3):237–244. doi: 10.1038/sj.ejhg.5200954. [DOI] [PubMed] [Google Scholar]
  5. Barton J. R., Gillon S., Ferguson A. Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-fold rise in Crohn's disease. Gut. 1989 May;30(5):618–622. doi: 10.1136/gut.30.5.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bayless T. M., Tokayer A. Z., Polito J. M., 2nd, Quaskey S. A., Mellits E. D., Harris M. L. Crohn's disease: concordance for site and clinical type in affected family members--potential hereditary influences. Gastroenterology. 1996 Sep;111(3):573–579. doi: 10.1053/gast.1996.v111.pm8780559. [DOI] [PubMed] [Google Scholar]
  7. Bonen Denise K., Cho Judy H. The genetics of inflammatory bowel disease. Gastroenterology. 2003 Feb;124(2):521–536. doi: 10.1053/gast.2003.50045. [DOI] [PubMed] [Google Scholar]
  8. Borgiani Paola, Vallo Laura, D'Apice Maria Rosaria, Giardina Emiliano, Pucci Sabina, Capon Francesca, Nisticò Steven, Chimenti Sergio, Pallone Francesco, Novelli Giuseppe. Exclusion of CARD15/NOD2 as a candidate susceptibility gene to psoriasis in the Italian population. Eur J Dermatol. 2002 Nov-Dec;12(6):540–542. [PubMed] [Google Scholar]
  9. Brant S. R., Fu Y., Fields C. T., Baltazar R., Ravenhill G., Pickles M. R., Rohal P. M., Mann J., Kirschner B. S., Jabs E. W. American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12. Gastroenterology. 1998 Nov;115(5):1056–1061. doi: 10.1016/s0016-5085(98)70073-3. [DOI] [PubMed] [Google Scholar]
  10. Brant S. R., Panhuysen C. I., Bailey-Wilson J. E., Rohal P. M., Lee S., Mann J., Ravenhill G., Kirschner B. S., Hanauer S. B., Cho J. H. Linkage heterogeneity for the IBD1 locus in Crohn's disease pedigrees by disease onset and severity. Gastroenterology. 2000 Dec;119(6):1483–1490. doi: 10.1053/gast.2000.20245. [DOI] [PubMed] [Google Scholar]
  11. Brophy S., Pavy S., Lewis P., Taylor G., Bradbury L., Robertson D., Lovell C., Calin A. Inflammatory eye, skin, and bowel disease in spondyloarthritis: genetic, phenotypic, and environmental factors. J Rheumatol. 2001 Dec;28(12):2667–2673. [PubMed] [Google Scholar]
  12. Calkins B. M. A meta-analysis of the role of smoking in inflammatory bowel disease. Dig Dis Sci. 1989 Dec;34(12):1841–1854. doi: 10.1007/BF01536701. [DOI] [PubMed] [Google Scholar]
  13. Cavanaugh J. A., Callen D. F., Wilson S. R., Stanford P. M., Sraml M. E., Gorska M., Crawford J., Whitmore S. A., Shlegel C., Foote S. Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16. Ann Hum Genet. 1998 Jul;62(Pt 4):291–298. doi: 10.1046/j.1469-1809.1998.6240291.x. [DOI] [PubMed] [Google Scholar]
  14. Cavanaugh J., IBD International Genetics Consortium International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn disease and chromosome 16. Am J Hum Genet. 2001 Apr 12;68(5):1165–1171. doi: 10.1086/320119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chamberlin W., Graham D. Y., Hulten K., El-Zimaity H. M., Schwartz M. R., Naser S., Shafran I., El-Zaatari F. A. Review article: Mycobacterium avium subsp. paratuberculosis as one cause of Crohn's disease. Aliment Pharmacol Ther. 2001 Mar;15(3):337–346. doi: 10.1046/j.1365-2036.2001.00933.x. [DOI] [PubMed] [Google Scholar]
  16. Cho J. H., Nicolae D. L., Gold L. H., Fields C. T., LaBuda M. C., Rohal P. M., Pickles M. R., Qin L., Fu Y., Mann J. S. Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7502–7507. doi: 10.1073/pnas.95.13.7502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Colombel J. F., Ferrari N., Debuysere H., Marteau P., Gendre J. P., Bonaz B., Soulé J. C., Modigliani R., Touze Y., Catala P. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000 Jun;118(6):1025–1030. doi: 10.1016/s0016-5085(00)70354-4. [DOI] [PubMed] [Google Scholar]
  18. Crane Alison M., Bradbury Linda, van Heel David A., McGovern Dermot P. B., Brophy Sinead, Rubin Laurence, Siminovitch Katherine A., Wordsworth B. Paul, Calin Andrei, Brown Matthew A. Role of NOD2 variants in spondylarthritis. Arthritis Rheum. 2002 Jun;46(6):1629–1633. doi: 10.1002/art.10329. [DOI] [PubMed] [Google Scholar]
  19. Cuthbert Andrew P., Fisher Sheila A., Mirza Muddassar M., King Kathy, Hampe Jochen, Croucher Peter J. P., Mascheretti Silvia, Sanderson Jeremy, Forbes Alastair, Mansfield John. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology. 2002 Apr;122(4):867–874. doi: 10.1053/gast.2002.32415. [DOI] [PubMed] [Google Scholar]
  20. D'Amato Mauro, Sorrentino Rosa, Pettersson Sven. The Crohn's associated NOD2 3020InsC frameshift mutation does not confer susceptibility to ankylosing spondylitis. J Rheumatol. 2002 Nov;29(11):2470–2471. [PubMed] [Google Scholar]
  21. Eaden J. A., Abrams K. R., Mayberry J. F. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001 Apr;48(4):526–535. doi: 10.1136/gut.48.4.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Elliman D. A., Bedford H. E. MMR vaccine--worries are not justified. Arch Dis Child. 2001 Oct;85(4):271–274. doi: 10.1136/adc.85.4.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Farmer R. G., Michener W. M., Mortimer E. A. Studies of family history among patients with inflammatory bowel disease. Clin Gastroenterol. 1980 May;9(2):271–277. [PubMed] [Google Scholar]
  24. Ferreiros-Vidal I., Garcia-Meijide J., Carreira P., Barros F., Carracedo A., Gomez-Reino J. J., Gonzalez A. The three most common CARD15 mutations associated with Crohn's disease and the chromosome 16 susceptibility locus for systemic lupus erythematosus. Rheumatology (Oxford) 2003 Apr;42(4):570–574. doi: 10.1093/rheumatology/keg192. [DOI] [PubMed] [Google Scholar]
  25. Ferreirós-Vidal Isabel, Amarelo Juan, Barros Francisco, Carracedo Angel, Gómez-Reino Juan J., Gonzalez Antonio. Lack of association of ankylosing spondylitis with the most common NOD2 susceptibility alleles to Crohn's disease. J Rheumatol. 2003 Jan;30(1):102–104. [PubMed] [Google Scholar]
  26. Ghosh S., Armitage E., Wilson D., Minor P. D., Afzal M. A. Detection of persistent measles virus infection in Crohn's disease: current status of experimental work. Gut. 2001 Jun;48(6):748–752. doi: 10.1136/gut.48.6.748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gutierrez Olga, Pipaon Carlos, Inohara Naohiro, Fontalba Ana, Ogura Yasunori, Prosper Felipe, Nunez Gabriel, Fernandez-Luna Jose L. Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. J Biol Chem. 2002 Aug 22;277(44):41701–41705. doi: 10.1074/jbc.M206473200. [DOI] [PubMed] [Google Scholar]
  28. Halfvarson Jonas, Bodin Lennart, Tysk Curt, Lindberg Eva, Järnerot Gunnar. Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology. 2003 Jun;124(7):1767–1773. doi: 10.1016/s0016-5085(03)00385-8. [DOI] [PubMed] [Google Scholar]
  29. Hampe J., Cuthbert A., Croucher P. J., Mirza M. M., Mascheretti S., Fisher S., Frenzel H., King K., Hasselmeyer A., MacPherson A. J. Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet. 2001 Jun 16;357(9272):1925–1928. doi: 10.1016/S0140-6736(00)05063-7. [DOI] [PubMed] [Google Scholar]
  30. Hampe J., Schreiber S., Shaw S. H., Lau K. F., Bridger S., Macpherson A. J., Cardon L. R., Sakul H., Harris T. J., Buckler A. A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort. Am J Hum Genet. 1999 Mar;64(3):808–816. doi: 10.1086/302294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Hart Ailsa L., Stagg Andrew J., Kamm Michael A. Use of probiotics in the treatment of inflammatory bowel disease. J Clin Gastroenterol. 2003 Feb;36(2):111–119. doi: 10.1097/00004836-200302000-00005. [DOI] [PubMed] [Google Scholar]
  32. Heliö T., Halme L., Lappalainen M., Fodstad H., Paavola-Sakki P., Turunen U., Färkkilä M., Krusius T., Kontula K. CARD15/NOD2 gene variants are associated with familially occurring and complicated forms of Crohn's disease. Gut. 2003 Apr;52(4):558–562. doi: 10.1136/gut.52.4.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hugot J. P., Chamaillard M., Zouali H., Lesage S., Cézard J. P., Belaiche J., Almer S., Tysk C., O'Morain C. A., Gassull M. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):599–603. doi: 10.1038/35079107. [DOI] [PubMed] [Google Scholar]
  34. Hugot J. P., Laurent-Puig P., Gower-Rousseau C., Olson J. M., Lee J. C., Beaugerie L., Naom I., Dupas J. L., Van Gossum A., Orholm M. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature. 1996 Feb 29;379(6568):821–823. doi: 10.1038/379821a0. [DOI] [PubMed] [Google Scholar]
  35. Hugot Jean-Pierre, Zouali Habib, Lesage Suzane. Lessons to be learned from the NOD2 gene in Crohn's disease. Eur J Gastroenterol Hepatol. 2003 Jun;15(6):593–597. doi: 10.1097/00042737-200306000-00003. [DOI] [PubMed] [Google Scholar]
  36. Inohara Naohiro, Ogura Yasunori, Fontalba Ana, Gutierrez Olga, Pons Fernando, Crespo Javier, Fukase Koichi, Inamura Seiichi, Kusumoto Shoichi, Hashimoto Masahito. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem. 2003 Jan 4;278(8):5509–5512. doi: 10.1074/jbc.C200673200. [DOI] [PubMed] [Google Scholar]
  37. Inoue Nagamu, Tamura Kazuo, Kinouchi Yoshitaka, Fukuda Yoshihiro, Takahashi Seiichi, Ogura Yasunori, Inohara Naohiro, Núez Gabriel, Kishi Yusuke, Koike Yuji. Lack of common NOD2 variants in Japanese patients with Crohn's disease. Gastroenterology. 2002 Jul;123(1):86–91. doi: 10.1053/gast.2002.34155. [DOI] [PubMed] [Google Scholar]
  38. Kabesch Michael, Peters Wilfried, Carr David, Leupold Wolfgang, Weiland Stephan K., von Mutius Erika. Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations. J Allergy Clin Immunol. 2003 Apr;111(4):813–817. doi: 10.1067/mai.2003.1336. [DOI] [PubMed] [Google Scholar]
  39. Laharie D., Debeugny S., Peeters M., Van Gossum A., Gower-Rousseau C., Bélaïche J., Fiasse R., Dupas J. L., Lerebours E., Piotte S. Inflammatory bowel disease in spouses and their offspring. Gastroenterology. 2001 Mar;120(4):816–819. doi: 10.1053/gast.2001.22574. [DOI] [PubMed] [Google Scholar]
  40. Lala Sanjay, Ogura Yasunori, Osborne Caroline, Hor Sok Ying, Bromfield Annabel, Davies Susan, Ogunbiyi Olagunju, Nuñez Gabriel, Keshav Satish. Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology. 2003 Jul;125(1):47–57. doi: 10.1016/s0016-5085(03)00661-9. [DOI] [PubMed] [Google Scholar]
  41. Lashner B. A., Shaheen N. J., Hanauer S. B., Kirschner B. S. Passive smoking is associated with an increased risk of developing inflammatory bowel disease in children. Am J Gastroenterol. 1993 Mar;88(3):356–359. [PubMed] [Google Scholar]
  42. Leong R. W. L., Armuzzi A., Ahmad T., Wong M. L., Tse P., Jewell D. P., Sung J. J. Y. NOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population. Aliment Pharmacol Ther. 2003 Jun 15;17(12):1465–1470. doi: 10.1046/j.1365-2036.2003.01607.x. [DOI] [PubMed] [Google Scholar]
  43. Lesage Suzanne, Zouali Habib, Cézard Jean-Pierre, Colombel Jean-Frédéric, Belaiche Jacques, Almer Sven, Tysk Curt, O'Morain Colm, Gassull Miquel, Binder Vibeke. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002 Mar 1;70(4):845–857. doi: 10.1086/339432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Linde Klaas van der, Boor Patrick P. C., Houwing-Duistermaat Jeanine J., Kuipers Ernst J., Wilson J. H. Paul, de Rooij Felix W. M. Card15 and Crohn's disease: healthy homozygous carriers of the 3020insC frameshift mutation. Am J Gastroenterol. 2003 Mar;98(3):613–617. doi: 10.1111/j.1572-0241.2003.07287.x. [DOI] [PubMed] [Google Scholar]
  45. Markowitz J., Grancher K., Rosa J., Aiges H., Daum F. Growth failure in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1993 May;16(4):373–380. doi: 10.1097/00005176-199305000-00005. [DOI] [PubMed] [Google Scholar]
  46. Mascheretti Silvia, Hampe Jochen, Croucher Peter J. P., Nikolaus Susanna, Andus Tilo, Schubert Silvia, Olson Allan, Bao Weihang, Fölsch Ulrich Robert, Schreiber Stefan. Response to infliximab treatment in Crohn's disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials. Pharmacogenetics. 2002 Oct;12(7):509–515. doi: 10.1097/00008571-200210000-00002. [DOI] [PubMed] [Google Scholar]
  47. Miceli-Richard C., Lesage S., Rybojad M., Prieur A. M., Manouvrier-Hanu S., Häfner R., Chamaillard M., Zouali H., Thomas G., Hugot J. P. CARD15 mutations in Blau syndrome. Nat Genet. 2001 Sep;29(1):19–20. doi: 10.1038/ng720. [DOI] [PubMed] [Google Scholar]
  48. Mirza Muddassar M., Fisher Sheila A., King Kathy, Cuthbert Andrew P., Hampe Jochen, Sanderson Jeremy, Mansfield John, Donaldson Peter, Macpherson Andrew J. S., Forbes Alastair. Genetic evidence for interaction of the 5q31 cytokine locus and the CARD15 gene in Crohn disease. Am J Hum Genet. 2003 Mar 3;72(4):1018–1022. doi: 10.1086/373880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Negoro K., McGovern D. P. B., Kinouchi Y., Takahashi S., Lench N. J., Shimosegawa T., Carey A., Cardon L. R., Jewell D. P., van Heel D. A. Analysis of the IBD5 locus and potential gene-gene interactions in Crohn's disease. Gut. 2003 Apr;52(4):541–546. doi: 10.1136/gut.52.4.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Newman Bill, Rubin Laurence A., Siminovitch Katherine A. NOD2/CARD15 gene mutation is not associated with susceptibility to Wegener's granulomatosis. J Rheumatol. 2003 Feb;30(2):305–307. [PubMed] [Google Scholar]
  51. O'Callaghan N. J., Adams K. E., van Heel D. A., Cavanaugh J. A. Association of TNF-alpha-857C with inflammatory bowel disease in the Australian population. Scand J Gastroenterol. 2003 May;38(5):533–534. [PubMed] [Google Scholar]
  52. Ogura Y., Bonen D. K., Inohara N., Nicolae D. L., Chen F. F., Ramos R., Britton H., Moran T., Karaliuskas R., Duerr R. H. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):603–606. doi: 10.1038/35079114. [DOI] [PubMed] [Google Scholar]
  53. Ogura Y., Inohara N., Benito A., Chen F. F., Yamaoka S., Nunez G. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem. 2000 Nov 21;276(7):4812–4818. doi: 10.1074/jbc.M008072200. [DOI] [PubMed] [Google Scholar]
  54. Ohmen J. D., Yang H. Y., Yamamoto K. K., Zhao H. Y., Ma Y., Bentley L. G., Huang Z., Gerwehr S., Pressman S., McElree C. Susceptibility locus for inflammatory bowel disease on chromosome 16 has a role in Crohn's disease, but not in ulcerative colitis. Hum Mol Genet. 1996 Oct;5(10):1679–1683. doi: 10.1093/hmg/5.10.1679. [DOI] [PubMed] [Google Scholar]
  55. Orchard T. R., Thiyagaraja S., Welsh K. I., Wordsworth B. P., Hill Gaston J. S., Jewell D. P. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology. 2000 Feb;118(2):274–278. doi: 10.1016/s0016-5085(00)70209-5. [DOI] [PubMed] [Google Scholar]
  56. Orchard Timothy R., Chua C. N., Ahmad Tariq, Cheng Hung, Welsh Kenneth I., Jewell Derek P. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology. 2002 Sep;123(3):714–718. doi: 10.1053/gast.2002.35396. [DOI] [PubMed] [Google Scholar]
  57. Orholm M., Binder V., Sørensen T. I., Rasmussen L. P., Kyvik K. O. Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand J Gastroenterol. 2000 Oct;35(10):1075–1081. doi: 10.1080/003655200451207. [DOI] [PubMed] [Google Scholar]
  58. Parkes M., Satsangi J., Lathrop G. M., Bell J. I., Jewell D. P. Susceptibility loci in inflammatory bowel disease. Lancet. 1996 Dec 7;348(9041):1588–1588. doi: 10.1016/S0140-6736(05)66204-6. [DOI] [PubMed] [Google Scholar]
  59. Probert C. S., Jayanthi V., Pinder D., Wicks A. C., Mayberry J. F. Epidemiological study of ulcerative proctocolitis in Indian migrants and the indigenous population of Leicestershire. Gut. 1992 May;33(5):687–693. doi: 10.1136/gut.33.5.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Rioux J. D., Daly M. J., Silverberg M. S., Lindblad K., Steinhart H., Cohen Z., Delmonte T., Kocher K., Miller K., Guschwan S. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001 Oct;29(2):223–228. doi: 10.1038/ng1001-223. [DOI] [PubMed] [Google Scholar]
  61. Rosenstiel Philip, Fantini Massimo, Bräutigam Karen, Kühbacher Tanja, Waetzig Georg H., Seegert Dirk, Schreiber Stefan. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology. 2003 Apr;124(4):1001–1009. doi: 10.1053/gast.2003.50157. [DOI] [PubMed] [Google Scholar]
  62. Roth M. P., Petersen G. M., McElree C., Feldman E., Rotter J. I. Geographic origins of Jewish patients with inflammatory bowel disease. Gastroenterology. 1989 Oct;97(4):900–904. doi: 10.1016/0016-5085(89)91495-9. [DOI] [PubMed] [Google Scholar]
  63. Roussomoustakaki Maria, Koutroubakis Ioannis, Vardas Em Manouel, Dimoulios Philippos, Kouroumalis Elias A., Baritaki Stavroula, Koutsoudakis George, Krambovitis Elias. NOD2 insertion mutation in a Cretan Crohn's disease population. Gastroenterology. 2003 Jan;124(1):272–274. doi: 10.1053/gast.2003.50036. [DOI] [PubMed] [Google Scholar]
  64. Rubin D. T., Hanauer S. B. Smoking and inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2000 Aug;12(8):855–862. doi: 10.1097/00042737-200012080-00004. [DOI] [PubMed] [Google Scholar]
  65. Satsangi J., Morecroft J., Shah N. B., Nimmo E. Genetics of inflammatory bowel disease: scientific and clinical implications. Best Pract Res Clin Gastroenterol. 2003 Feb;17(1):3–18. doi: 10.1053/bega.2002.0349. [DOI] [PubMed] [Google Scholar]
  66. Satsangi J., Parkes M., Louis E., Hashimoto L., Kato N., Welsh K., Terwilliger J. D., Lathrop G. M., Bell J. I., Jewell D. P. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet. 1996 Oct;14(2):199–202. doi: 10.1038/ng1096-199. [DOI] [PubMed] [Google Scholar]
  67. Satsangi J., Welsh K. I., Bunce M., Julier C., Farrant J. M., Bell J. I., Jewell D. P. Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet. 1996 May 4;347(9010):1212–1217. doi: 10.1016/s0140-6736(96)90734-5. [DOI] [PubMed] [Google Scholar]
  68. Sawcer S., Maranian M., Hensiek A., Roxburgh R., Gray J., Compston A. Crohn's associated NOD2 gene variants are not involved in determining susceptibility to multiple sclerosis. J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1157–1157. doi: 10.1136/jnnp.74.8.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Sawczenko A., Sandhu B. K., Logan R. F., Jenkins H., Taylor C. J., Mian S., Lynn R. Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet. 2001 Apr 7;357(9262):1093–1094. doi: 10.1016/s0140-6736(00)04309-9. [DOI] [PubMed] [Google Scholar]
  70. Sellon R. K., Tonkonogy S., Schultz M., Dieleman L. A., Grenther W., Balish E., Rennick D. M., Sartor R. B. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998 Nov;66(11):5224–5231. doi: 10.1128/iai.66.11.5224-5231.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Steer S., Fisher S. A., Fife M., Cuthbert A., Newton J., Wordsworth P., Lewis C. M., Mathew C. G., Lanchbury J. S. Development of rheumatoid arthritis is not associated with two polymorphisms in the Crohn's disease gene CARD15. Rheumatology (Oxford) 2003 Feb;42(2):304–307. doi: 10.1093/rheumatology/keg091. [DOI] [PubMed] [Google Scholar]
  72. Thompson N. P., Driscoll R., Pounder R. E., Wakefield A. J. Genetics versus environment in inflammatory bowel disease: results of a British twin study. BMJ. 1996 Jan 13;312(7023):95–96. doi: 10.1136/bmj.312.7023.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Tysk C., Lindberg E., Järnerot G., Flodérus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988 Jul;29(7):990–996. doi: 10.1136/gut.29.7.990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Vermeire Severine, Louis Edouard, Rutgeerts Paul, De Vos Martine, Van Gossum Andre, Belaiche Jacques, Pescatore Paul, Fiasse Rene, Pelckmans Paul, Vlietinck Robert. NOD2/CARD15 does not influence response to infliximab in Crohn's disease. Gastroenterology. 2002 Jul;123(1):106–111. doi: 10.1053/gast.2002.34172. [DOI] [PubMed] [Google Scholar]
  75. Vermeire Severine, Wild Gary, Kocher Kerry, Cousineau Josee, Dufresne Line, Bitton Alain, Langelier Diane, Pare Pierre, Lapointe Gilles, Cohen Albert. CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structure. Am J Hum Genet. 2002 May 17;71(1):74–83. doi: 10.1086/341124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Winslet M. C., Allan A., Poxon V., Youngs D., Keighley M. R. Faecal diversion for Crohn's colitis: a model to study the role of the faecal stream in the inflammatory process. Gut. 1994 Feb;35(2):236–242. doi: 10.1136/gut.35.2.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. van Heel David A., Udalova Irina A., De Silva Arjuna P., McGovern Dermot P., Kinouchi Yoshitaka, Hull Jeremy, Lench Nicholas J., Cardon Lon R., Carey Alisoun H., Jewell Derek P. Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF(-kappa)B transcription factors. Hum Mol Genet. 2002 May 15;11(11):1281–1289. doi: 10.1093/hmg/11.11.1281. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES