Skip to main content
SpringerLink
Log in

Genetics

  • Chapter
Crohn’s Disease

Part of the book series: Updates in Surgery ((UPDATESSURG))

  • 2153 Accesses

Abstract

In the last few years, the application of molecular studies in medicine has dramatically increased our knowledge of the biological basis of human diseases. This is evident not only for rare single-gene disorders, but also for many common disorders, including Crohn’s disease (CD).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cho JH (2008) The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 8:458–66

    Article  PubMed  CAS  Google Scholar 

  2. Geboes K, Colombel JF, Greenstein A et al (2008) Pathology Task Force of the International Organization of Inflammatory Bowel Diseases. Indeterminate colitis: a review of the concept—what’s in a name? Inflamm Bowel Dis 14:850–857

    Article  PubMed  Google Scholar 

  3. Cho JH, Weaver CT (2007) The genetics of inflammatory bowel disease. Gastroenterology 133:1327–1339

    Article  PubMed  CAS  Google Scholar 

  4. Shivananda S, Lennard-Jones J, Logan R et al (1996) Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). Gut 39:690–697

    Article  PubMed  CAS  Google Scholar 

  5. Frangos CC, Frangos CC (2007) Inflammatory bowel disease: reviewing an old study under a new perspective. Gut 56:1638–1639

    PubMed  Google Scholar 

  6. Yang H, Taylor KD, Rotter JI (2001) Inflammatory bowel disease. I. Genetic epidemiology. Mol Genet Metab 74:1–21

    Article  PubMed  CAS  Google Scholar 

  7. Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK (2008) An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol 103:3167–3182

    Article  PubMed  Google Scholar 

  8. Andres PG, Friedman LS (1999) Epidemiology and the natural course of inflammatory bowel disease. Gastroenterol Clin North Am 28:255–281

    Article  PubMed  CAS  Google Scholar 

  9. Satsangi J, Jewell DP, Bell JI (1997) The genetics of inflammatory bowel disease. Gut 40:572–574

    PubMed  CAS  Google Scholar 

  10. Binder V (1998) Genetic epidemiology in inflammatory bowel disease. Dig Dis 16:351–355

    Article  PubMed  CAS  Google Scholar 

  11. Tysk C, Lindberg E. Järnerot G et al (1988) 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 29:990–996

    Article  PubMed  CAS  Google Scholar 

  12. Thompson NP, Driscoll R, Pounder RE, Wakefield AJ (1996) Genetics versus environment in inflammatory bowel disease: results of a British twin study. BMJ 312:95–96

    PubMed  CAS  Google Scholar 

  13. Orholm M, Binder V, Sørensen TI et al (2000) Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand J Gastroenterol 35:1075–1081

    Article  PubMed  CAS  Google Scholar 

  14. Halfvarson J, Bodin L, Tysk C et al (2003) Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology 124:1767–1773

    Article  PubMed  Google Scholar 

  15. Duerr RH, Taylor KD, Brant SR et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463

    Article  PubMed  CAS  Google Scholar 

  16. Fisher SA, Tremelling M, Anderson CA et al (2008) Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn’s disease. Nat Genet 40:710–712

    Article  PubMed  CAS  Google Scholar 

  17. Cho JH, Nicolae DL, Gold LH et al (1998) 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 95:7502–7507

    Article  PubMed  CAS  Google Scholar 

  18. Fowler EV, Eri R, Hume G et al (2005) TNFal pha and IL 10 SNPs act together to predict disease behaviour in Crohn’s disease. J Med Genet 42:523–528

    Article  PubMed  CAS  Google Scholar 

  19. Villani AC, Lemire M, Fortin G et al (2009) Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility. Nat Genet 41:71–76

    Article  PubMed  CAS  Google Scholar 

  20. Nemetz A, Köpe A, Molnár T et al (1999) Significant differences in the interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in a Hungarian population with inflammatory bowel disease. Scand J Gastroenterol 34:175–179

    Article  PubMed  CAS  Google Scholar 

  21. Hampe J, Franke A, Rosenstiel P et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211

    Article  PubMed  CAS  Google Scholar 

  22. Paavola P, Heliö T, Kiuru M et al (2001) Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21. Eur J Hum Genet 9:328–334

    Article  PubMed  CAS  Google Scholar 

  23. Barrett JC, Hansoul S, Nicolae DL et al (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962

    Article  PubMed  CAS  Google Scholar 

  24. Török HP, Glas J, Tonenchi L et al (2004) Crohn’s disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology 127:365–366

    Article  PubMed  Google Scholar 

  25. Duerr RH, Barmada MM, Zhang L et al (2002) Evidence for an inflammatory bowel disease locus on chromosome 3p26: linkage, transmission/disequilibrium and partitioning of linkage. Hum Mol Genet 11:2599–2606

    Article  PubMed  CAS  Google Scholar 

  26. Pierik M, Joossens S, Van Steen K et al (2006) Toll-like receptor-1,-2, and-6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 12:1–8

    Article  PubMed  Google Scholar 

  27. Karban AS, Okazaki T, Panhuysen CI et al (2004) Functional annotation of a novel NFKB1 promoter polymorphism that increases risk for ulcerative colitis. Hum Mol Genet 13:35–45

    Article  PubMed  CAS  Google Scholar 

  28. Libioulle C, Louis E, Hansoul S et al (2007) Novel Crohn disease locus identified by genomewide association maps to a gene desert on 5p13. 1 and modulates expression of PTGER4. PLoS Genet 3:e58

    Article  PubMed  CAS  Google Scholar 

  29. Franke A, Balschun T, Karlsen TH et al (2008) Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet 40:713–715

    Article  PubMed  CAS  Google Scholar 

  30. Peltekova VD, Wintle RF, Rubin LA et al (2004) Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 36:471–475

    Article  PubMed  CAS  Google Scholar 

  31. Silverberg MS, Duerr RH, Brant SR et al; NIDDK IBD Genetics Consortium (2007) Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn’s disease. Eur J Hum Genet 15:328–335

    Article  PubMed  CAS  Google Scholar 

  32. Parkes M, Barrett JC, Prescott NJ et al (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 39:830–832

    Article  PubMed  CAS  Google Scholar 

  33. Bouma G, Xia B, Crusius JB et al (1996) Distribution of four polymorphisms in the tumour necrosis factor (TNF) genes in patients with inflammatory bowel disease (IBD). Clin Exp Immunol 103:391–396

    PubMed  CAS  Google Scholar 

  34. Stokkers PC, Reitsma PH, Tytgat GN, van Deventer SJ (1999) HLA-DR and-DQ phenotypes in inflammatory bowel disease: a meta-analysis. Gut 45:395–401

    PubMed  CAS  Google Scholar 

  35. Orchard TR, Dhar A, Simmons JD et al (2001) MHC class I chain-like gene A (MICA) and its associations with inflammatory bowel disease and peripheral arthropathy. Clin Exp Immunol 126:437–440

    Article  PubMed  CAS  Google Scholar 

  36. McGovern DP, Hysi P, Ahmad T et al (2005) Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet 14:1245–1250

    Article  PubMed  CAS  Google Scholar 

  37. Cantor MJ, Nickerson P, Bernstein CN (2005) The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease. Am J Gastroenterol 100:1134–1142

    Article  PubMed  CAS  Google Scholar 

  38. Brant SR, Panhuysen CI, Nicolae D et al (2003) MDRI Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet 73:1282–1292

    Article  PubMed  CAS  Google Scholar 

  39. Kyo K, Muto T, Nagawa H et al (2001) Associations of distinct variants of the intestinal mucin gene MUC3A with ulcerative colitis and Crohn’s disease. J Hum Genet 46:5–20

    Article  PubMed  CAS  Google Scholar 

  40. Dideberg V, Kristjansdottir G, Milani L et al (2007) An insertion-deletion polymorphism in the interferon regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases. Hum Mol Genet 16:3008–3016

    Article  PubMed  CAS  Google Scholar 

  41. Yamazaki K, McGovern D, Ragoussis J et al (2005) Single nucleotide polymorphisms in TN-FSF15 confer susceptibility to Crohn’s disease. Hum Mol Genet 14:3499–3506

    Article  PubMed  CAS  Google Scholar 

  42. Franchimont D, Vermeire S, El Housni H et al (2004) Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis. Gut 53:987–992

    Article  PubMed  CAS  Google Scholar 

  43. Rioux JD, Xavier RJ, Taylor KD et al (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39:596–604

    Article  PubMed  CAS  Google Scholar 

  44. Stoll M, Corneliussen B, Costello CM et al (2004) Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 36:476–80

    Article  PubMed  CAS  Google Scholar 

  45. Tamura K, Fukuda Y, Sashio H et al (2002) IL18 polymorphism is associated with an increased risk of Crohn’s disease. J Gastroenterol 37 (Suppl 14):111–116

    PubMed  CAS  Google Scholar 

  46. Yang H, Ohmen JD, Ma Y et al (1999) Additional evidence of linkage between Crohn’s disease and a putative locus on chromosome 12. Genet Med 1:194–198

    PubMed  CAS  Google Scholar 

  47. Duerr RH, Barmada MM, Zhang L et al (2000) High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12. Am J Hum Genet 66:1857–1862

    Article  PubMed  CAS  Google Scholar 

  48. Glas J, Török HP, Unterhuber H et al (2003) The-295T-to-C promoter polymorphism of the IL-16 gene is associated with Crohn’s disease. Clin Immunol 106:197–200

    Article  PubMed  CAS  Google Scholar 

  49. Hampe J, Frenzel H, Mirza MM et al (2002) Evidence for a NOD2-independent susceptibility locus for inflammatory bowel disease on chromosome 16p. Proc Natl Acad Sci U S A 99:321–326

    Article  PubMed  CAS  Google Scholar 

  50. Hampe J, Cuthbert A, Croucher PJ et al (2001) Association between insertion mutation in NOD2 gene and Crohn’s disease in German and British populations. Lancet 357:1925–1928

    Article  PubMed  CAS  Google Scholar 

  51. Hugot JP, Chamaillard M, Zouali H et al (2001) Association of NOD2 leucine-rich repeat vari-with susceptibility to Crohn’s disease. Nature 411:599–603

    Article  PubMed  CAS  Google Scholar 

  52. Rioux JD, Silverberg MS, Daly MJ et al (2000) Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet 66:1863–1870

    Article  PubMed  CAS  Google Scholar 

  53. Latiano A, Palmieri O, Valvano MR et al (2008) The association of MYO9B gene in Italian patients with inflammatory bowel diseases. Aliment Pharmacol Ther 27:241–248

    Article  PubMed  CAS  Google Scholar 

  54. McGovern DP, Butler H, Ahmad T et al (2006) TUCAN (CARD8) genetic variants and inflammatory bowel disease. Gastroenterology 131:1190–1196

    Article  PubMed  CAS  Google Scholar 

  55. Ogura Y, Bonen DK, Inohara N et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    Article  PubMed  CAS  Google Scholar 

  56. Inohara N, Ogura Y, Fontalba A et al (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 278:5509–5512

    Article  PubMed  CAS  Google Scholar 

  57. Kobayashi KS, Chamaillard M, Ogura Y et al (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307:731–734

    Article  PubMed  CAS  Google Scholar 

  58. Cavanaugh JA, Adams KE, Quak EJ et al (2003) CARD15/NOD2 risk alleles in the development of Crohn’s disease in the Australian population. Ann Hum Genet 67:35–41

    Article  PubMed  CAS  Google Scholar 

  59. Yamazaki K, Takazoe M, Tanaka T et al (2002) Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with Crohn’s disease. J Hum Genet 47:469–472

    Article  PubMed  CAS  Google Scholar 

  60. Croucher PJ, Mascheretti S, Hampe J et al (2003) Haplotype structure and association to Crohn’s disease of CARD15 mutations in two ethnically divergent populations. Eur J Hum Genet 11:6–16

    Article  PubMed  CAS  Google Scholar 

  61. Leong RW, Armuzzi A, Ahmad T et al (2003) NOD2/CARD15 gene polymorphisms and Crohn’s disease in the Chinese population. Aliment Pharmacol Ther 17:1465–1470

    Article  PubMed  CAS  Google Scholar 

  62. Kugathasan S, Loizides A, Babusukumar U et al (2005) Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and White children with Crohn’s disease. Inflamm Bowel Dis 11:631–638

    Article  PubMed  Google Scholar 

  63. Economou M, Trikalinos TA, Loizou KT et al (2004) Differential effects of N0D2 variants on Crohn’s disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol 99:2393–2404

    Article  PubMed  CAS  Google Scholar 

  64. Annese V, Lombardi G, Perri F et al (2005) Variants of CARD15 are associated with an aggressive clinical course of Crohn’s disease — an IG-IBD study. Am J Gastroenterol 100:84–92

    Article  PubMed  CAS  Google Scholar 

  65. Crawford NP, Colliver DW, Eichenberger MR et al (2007) CARD15 genotype-phenotype relationships in a small inflammatory bowel disease population with severe disease affection status. Dig Dis Sci 52:2716–2724

    Article  PubMed  CAS  Google Scholar 

  66. Wiekowski MT, Leach MW, Evans EW et al (2001) Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol 166:7563–7570

    PubMed  CAS  Google Scholar 

  67. Yen D, Cheung J, Scheerens H et al (2006) IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 116:1310–1316

    Article  PubMed  CAS  Google Scholar 

  68. Cummings SA, Rubin DT (2006) The complexity and challenges of genetic counseling and testing for inflammatory bowel disease. J Genet Couns 15:465–476

    Article  PubMed  Google Scholar 

  69. Lindberg E, Tysk C, Andersson K, Järnerot G (1988) Smoking and inflammatory bowel disease. A case control study. Gut 29:352–357

    CAS  Google Scholar 

  70. Calkins BM (1989) A meta-analysis of the role of smoking in inflammatory bowel disease. Dig Dis Sci 34:1841–1854

    Article  PubMed  CAS  Google Scholar 

  71. Sandler RS, Wurzelmann JL, Lyles CM (1992) Oral contraceptive use and the risk of inflammatory bowel disease. Epidemiology 3:374–378

    Article  PubMed  CAS  Google Scholar 

  72. Brant SR, Picco MF, Achkar JP et al (2003) Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn’s disease phenotypes. Inflamm Bowel Dis 9:281–289

    Article  PubMed  Google Scholar 

  73. Gleason TR, Evans ME (2004) Perceived vulnerability: a comparison of parents and children. J Child Health Care 8:279–287

    Article  PubMed  Google Scholar 

  74. Grosse SD, Khoury MJ (2006) What is the clinical utility of genetic testing? Genet Med 8:448–450

    Article  PubMed  Google Scholar 

  75. Pierik M, Rutgeerts P, Vlietinck R, Vermeire S (2006) Pharmacogenetics in inflammatory bowel disease. World J Gastroenterol 12:3657–3667

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Sapienza University, San Camillo-Forlamini Hospital, Rome, Italy

    Marco Castori & Paola Grammatico

Authors
  1. Marco Castori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paola Grammatico
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgery, San Camillo-Forlanini Hospital, Rome, Italy

    Roberto Tersigni (Chief and Chairman) (Chief and Chairman)

  2. Gastroenterology Unit, San Camillo-Forlanini Hospital, Rome, Italy

    Cosimo Prantera (Professor Emeritus) (Professor Emeritus)

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Italia

About this chapter

Cite this chapter

Castori, M., Grammatico, P. (2010). Genetics. In: Tersigni, R., Prantera, C. (eds) Crohn’s Disease. Updates in Surgery. Springer, Milano. https://doi.org/10.1007/978-88-470-1472-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-88-470-1472-5_3

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-1471-8

  • Online ISBN: 978-88-470-1472-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation