Skip to main content

Advertisement

SpringerLink
Log in

Genotype and phenotype relation in inflammatory bowel disease

  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Summary

Genotype-phenotype analysis helps us to discriminate among various subgroups of IBD and consequently helps us to understand the etiology and pathogenesis as well as develop effective treatments for each subgroup of IBD.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. McConnell R, Vadheim C. Inflammatory bowel disease. Oxford: Oxford University Press; 1992. p. 326–48.

    Google Scholar 

  2. Tysk C, Lindberg E, Jarnerot G, Floderus-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; 29: 990–6.

    Article  PubMed  CAS  Google Scholar 

  3. Satsangi J, Jewell DP, Rosenberg WM, Bell JI. Genetics of inflammatory bowel disease. Gut 1994; 35: 696–700.

    Article  PubMed  CAS  Google Scholar 

  4. Yang H, Rotter JI. Genetics of inflammatory bowel disease. In: Targan SR, Shanahan F, eds. Inflammatory bowel disease: from bench to bedside. Baltimore: Williams & Wilkins; 1994. p. 32–64.

    Google Scholar 

  5. Orholm M, Munkholm P, Langholz E, Nielsen OH, Sorensen IA, Binder V. Familial occurrence of inflammatory bowel disease. N Engl J Med 1991; 324: 84–8.

    PubMed  CAS  Google Scholar 

  6. Probert CS, Jayanthi V, Hughes AO, Thompson JR, Wicks AC, Mayberry JF. Prevalence and family risk of ulcerative colitis and Crohn’s disease: an epidemiological study among Europeans and south Asians in Leicestershire. Gut 1993; 34: 1547–51.

    Article  PubMed  CAS  Google Scholar 

  7. Kuster W, Pascoe L, Purrmann J, Funk S, Majewski F. The genetics of Crohn disease: complex segregation analysis of a family study with 265 patients with Crohn disease and 5387 relatives. Am J Med Genet 1989; 32: 105–8.

    Article  PubMed  CAS  Google Scholar 

  8. Hugot JP, Cho JH. Update on genetics of inflammatory bowel disease. Curr Opin Gastroenterol 2002;18: 410–5.

    Article  PubMed  CAS  Google Scholar 

  9. Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, et al. Mapping of a susceptibility locus for Crohn’s disease on chromosome 16. Nature (Lond) 1996; 379: 821–3.

    Article  CAS  Google Scholar 

  10. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature (Lond) 2001; 411: 603–6.

    Article  CAS  Google Scholar 

  11. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature (Lond) 2001; 411: 599–603.

    Article  CAS  Google Scholar 

  12. Hampe J, Cuthbert A, Croucher PJ, Mirza MM, Mascheretti S, Fisher S, et al. Association between insertion mutation in NOD2 gene and Crohn’s disease in German and British populations. Lancet 2001; 357: 1925–8.

    Article  PubMed  CAS  Google Scholar 

  13. Satsangi J, Parkes M, Louis E, Hashimoto L, Kato N, Welsh K, et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3,7 and 12. Nat Genet 1996;14: 199–202.

    Article  PubMed  CAS  Google Scholar 

  14. Duerr RH, Barmada MM, Zhang L, Davis S, Preston RA, Chensny LJ, et al. Linkage and association between inflammatory bowel disease and a locus on chromosome 12. Am J Hum Genet 1998; 63: 95–100.

    Article  PubMed  CAS  Google Scholar 

  15. Yang H, Ohmen JD, Ma Y, Bentley LG, Targan SR, Fischel-Ghodsian N, Rotter JI. Additional evidence of linkage between Crohn’s disease and a putative locus on chromosome 12. Genet Med 1999; l: 194–8.

    Google Scholar 

  16. Curran ME, Lau KF, Hampe J, Schreiber S, Bridger S, Macpherson AJ, et al. Genetic analysis of inflammatory bowel disease in a large European cohort supports linkage to chromosomes 12 and 16. Gastroenterology 1998; 115: 1066–71.

    Article  PubMed  CAS  Google Scholar 

  17. Yang H, Plevy SE, Taylor K, Tyan D, Fischel-Ghodsian N, McElree C, et al. Linkage of Crohn’s disease to the major histocompatibility complex region is detected by multiple nonparametric analyses. Gut 1999; 44: 519–26.

    Article  PubMed  CAS  Google Scholar 

  18. Hampe J, Shaw SH, Saiz R, Leysens N, Lantermann A, Mascheretti S, et al. Linkage of inflammatory bowel disease to human chromosome 6p. Am J Hum Genet 1999; 65: 1647–55.

    Article  PubMed  CAS  Google Scholar 

  19. Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, McLeod RS, Griffiths AM, et al. Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet 2000; 66: 1863–70.

    Article  PubMed  CAS  Google Scholar 

  20. Dechairo B, Dimon C, van Heel D, Mackay I, Edwards M, Scambler P, et al. Replication and extension studies of inflammatory bowl disease susceptibility regions confirm linkage to chromosome 6p (IBD3). Eur J Hum Genet 2001; 9: 627–33.

    Article  PubMed  CAS  Google Scholar 

  21. Ma Y, Ohmen JD, Li Z, Bentley LG, McElree C, Pressman S, et al. A genome-wide search identifies potential new susceptibility loci for Crohn’s disease. Inflamm Bowel Dis 1999; 5: 271–8.

    PubMed  CAS  Google Scholar 

  22. Duerr RH, Barmada MM, Zhang L, Pfutzer R, Weeks DE. Highdensity genome scan in Crohn disease shows confirmed linkage to chromosome 14qll-12. Am J Hum Genet 2000; 66: 1857–62.

    Article  PubMed  CAS  Google Scholar 

  23. Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet 2001; 29: 223–8.

    Article  PubMed  CAS  Google Scholar 

  24. Cho JH, Nicolae DL, Gold LH, Fields CT, LaBuda MC, Rohal PM, et al. Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between lp and IBD1. Proc Natl Acad Sci U S A 1998; 95: 7502–7.

    Article  PubMed  CAS  Google Scholar 

  25. Hampe J, Frenzel H, Mirza MM, Croucher PJ, Cuthbert A, Mascheretti S, et al. Evidence for a NOD2-independent susceptibility locus for inflammatory bowel disease on chromosome 16p. Proc Natl Acad Sci U S A 2002; 99: 321–6.

    Article  PubMed  CAS  Google Scholar 

  26. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 2003; 278: 5509–12.

    Article  PubMed  CAS  Google Scholar 

  27. Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y, et al. Lack of common NOD2 variants in Japanese patients with Crohn’s disease. Gastroenterology 2002; 123: 86–91.

    Article  PubMed  CAS  Google Scholar 

  28. Sugimura M, Kinouchi Y, Takahashi S, Aihara H, Takagi S, Negoro K, et al. CARD15/NOD2 mutational analysis in Japanese patients with Crohn’s disease. Clin Genet 2003; 63: 160–2.

    Article  PubMed  CAS  Google Scholar 

  29. Yamazaki K, Takazoe M, Tanaka T, Kazumori T, Nakamura Y. Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with Crohn’s disease. J Hum Genet 2002; 47: 469–72.

    Article  PubMed  CAS  Google Scholar 

  30. Giallourakis C, Stoll M, Miller K, Hampe J, Lander ES, Daly MJ, et al. IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis. Am J Hum Genet 2003; 73: 205–11.

    Article  PubMed  CAS  Google Scholar 

  31. McGovern DP, Van Heel DA, Negoro K, Ahmad T, Jewell DP. Further evidence of IBD5/CARD15 (NOD2) epistasis in the susceptibility to ulcerative colitis. Am J Hum Genet 2003; 73: 1465–6.

    Article  PubMed  CAS  Google Scholar 

  32. Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 2004; 36: 471–5.

    Article  PubMed  CAS  Google Scholar 

  33. Ahmad T, Armuzzi A, Bunce M, Mulcahy-Hawes K, Marshall SE, Orchard TR, et al. The molecular classification of the clinical manifestations of Crohn’s disease. Gastroenterology 2002;122: 854–66.

    Article  PubMed  CAS  Google Scholar 

  34. Cuthbert AP, Fisher SA, Mirza MM, King K, Hampe J, Croucher PJ, et al. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology 2002; 122: 867–74.

    Article  PubMed  CAS  Google Scholar 

  35. Lesage S, Zouali H, Cezard JP, Colombel JF, Belaiche J, Almer S, et al. CARD15/NOD2 mutational analysis and genotypephenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet 2002; 70: 845–57.

    Article  PubMed  CAS  Google Scholar 

  36. Mendoza JL, Murillo LS, Fernandez L, Pena AS, Lana R, Ureclay E, et al. Prevalence of mutations of the NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn disease. Scand J Gastroenterol 2003; 38: 1235–40.

    Article  PubMed  CAS  Google Scholar 

  37. Hampe J, Grebe J, Nikolaus S, Solberg C, Croucher PJ, Mascheretti S, et al. Association of NOD2 (CARD 15) genotype with clinical course of Crohn’s disease: a cohort study. Lancet 2002; 359: 1661–5.

    Article  PubMed  CAS  Google Scholar 

  38. Fidder HH, Olschwang S, Avidan B, Zouali H, Lang A, Bardan E, et al. Association between mutations in the CARD15 (NOD2) gene and Crohn’s disease in Israeli Jewish patients. Am J Med Genet 2003; 121A: 240–4.

    Article  PubMed  Google Scholar 

  39. Armuzzi A, Ahmad T, Ling KL, de Silva A, Cullen S, van Heel D, et al. Genotype-phenotype analysis of the Crohn’s disease susceptibility haplotype on chromosome 5q31. Gut 2003; 52: 1133–9.

    Article  PubMed  CAS  Google Scholar 

  40. Asakura H, Tsuchiya M, Aiso S, Watanabe M, Kobayashi K, Hibi T, et al. Association of the human lymphocyte-DR2 antigen with Japanese ulcerative colitis. Gastroenterology 1982; 82: 413–8.

    PubMed  CAS  Google Scholar 

  41. Toyoda H, Wang SJ, Yang HY, Redford A, Magalong D, Tyan D, et al. Distinct associations of HLA class II genes with inflammatory bowel disease. Gastroenterology 1993; 104: 741–8.

    PubMed  CAS  Google Scholar 

  42. Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, Targan S, et al. Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology 1997;112: 1845–53.

    Article  PubMed  CAS  Google Scholar 

  43. Yoshitake S, Kimura A, Okada M, Yao T, Sasazuki T. HLA class II alleles in Japanese patients with inflammatory bowel disease. Tissue Antigens 1999; 53: 350–8.

    Article  PubMed  CAS  Google Scholar 

  44. Nakajima A, Matsuhashi N, Kodama T, Yazaki Y, Takazoe M, Kimura A. HLA-linked susceptibility and resistance genes in Crohn’s disease. Gastroenterology 1995; 109: 1462–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Sciryo, Aoba, 980-8574, Sendai, Japan

    Yoshitaka Kinouchi, Kenichi Negoro, Sho Takagi, Sciichi Takahashi & Tooru Shimosegawa

Authors
  1. Yoshitaka Kinouchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenichi Negoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sho Takagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sciichi Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tooru Shimosegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kinouchi, Y., Negoro, K., Takagi, S. et al. Genotype and phenotype relation in inflammatory bowel disease. J Gastroenterol 40 (Suppl 16), 21–24 (2005). https://doi.org/10.1007/BF02990574

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02990574

Key words

Search

Navigation