Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Current status of genetics research in inflammatory bowel disease

Genes & Immunity volume 6, pages 637–645 (2005)Cite this article

Abstract

The research on genetic susceptibility of inflammatory bowel diseases (IBD) has been tremendous and over 10 chromosomal regions have been identified by genome-wide scanning. Further fine mapping as well as candidate gene studies have already led to the identification of a number of susceptibility genes including CARD15, DLG5, OCTN1 and 2, NOD1, HLA, and TLR4. The CARD15 gene is undoubtedly replicated most widely and most understood at present. CARD15 is involved in the recognition of bacterial peptidoglycan-derived muramyl dipeptide (MDP) and will stimulate secretion of antimicrobial peptides including alpha-defensins (also called cryptdins) to protect the host from invasion. Genetic research in IBD has advanced our understanding of the clinical heterogeneity of the disease and has started to tackle the complex interactions between genetic risk factors and environmental risk factors in IBD. Genes also interfere with the metabolization of drugs and may influence the clinical response and the drug-related toxicity. Interesting pharmacogenetic data with respect to steroids, azathioprine, and infliximab have been generated in IBD. Overall, it is anticipated that genetic markers in the future will be implemented in an integrated molecular diagnostic and prognostic approach of our patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Roth MP, Petersen GM, McElree C et al. Geographic origins of Jewish patients with inflammatory bowel disease. Gastroenterology 1989; 97: 900–904.

    CAS  PubMed  Google Scholar 

  2. Yang H, McElree C, Shanahan F et al. Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews. Gut 1993; 34: 517–524.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Orholm M, Munkholm P, Langholz E et al. Familial occurrence of inflammatory bowel disease. N Engl J Med 1991; 324: 84–88.

    Article  CAS  PubMed  Google Scholar 

  4. Peeters M, Nevens H, Baert F et al. Familial aggregation in Crohn's disease: increased age-adjusted risk and concordance in clinical characteristics. Gastroenterology 1996; 111: 597–603.

    CAS  PubMed  Google Scholar 

  5. Satsangi J, Rosenberg W, Jewell DP . The prevalence of inflammatory bowel disease in relatives of patients with Crohn's disease. Eur J Gastroenterol Hepatol 1994; 6: 413–416.

    Google Scholar 

  6. Laharie D, Debeugny S, Peeters M et al. Inflammatory bowel disease in spouses and their offspring. Gastroenterology 2001; 120: 816–819.

    CAS  PubMed  Google Scholar 

  7. Tysk C, Lindberg E, Jarnerot G et al. 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: 990–996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Thompson NP, Driscoll R, Pounder RE et al. Genetic versus environment in inflammatory bowel disease: results of a British Twin Study. BMJ 1996; 312: 95–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Orholm M, Binder V, Sorensen TI, Rasmussen LP, Kyvik KO . Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand J Gastroenterol 2000; 35: 1075–1081.

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  11. Vermeire S, Peeters M, Vlietinck R et al. Anti-Saccharomyces cerevisiae antibodies (ASCA), phenotypes of IBD, and intestinal permeability: a study in IBD families. Inflamm Bowel Dis 2001; 7: 8–15.

    CAS  PubMed  Google Scholar 

  12. Shanahan F, Duerr R, Rotter JI . Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity. Gastroenterology 1992; 103: 456–461.

    CAS  PubMed  Google Scholar 

  13. Bouma G, Crusius JB, Garcia-Gonzalez MA et al. Genetic markers in clinically well defined patients with ulcerative colitis (UC). Clin Exp Immunol 1999; 115: 294–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Seibold F, Slametschka D, Gregor M et al. Neutrophil autoantibodies: a genetic marker in primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 1994; 107: 532–536.

    CAS  PubMed  Google Scholar 

  15. Sendid B, Quinton JF, Charrier G et al. Anti-Saccharomyces cerevisiae mannan antibodies in familial Crohn's disease. Am J Gastroenterol 1998; 93: 1306–1310.

    CAS  PubMed  Google Scholar 

  16. Landers CJ, Cohavy O, Misra R et al. Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens. Gastroenterology 2002; 123: 689–699.

    CAS  PubMed  Google Scholar 

  17. Mow WS, Vasiliauskas EA, Lin YC et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology 2004; 126: 414–424.

    CAS  PubMed  Google Scholar 

  18. Lodes MJ, Cong Y, Elson CO et al. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 2004; 113: 1296–1306.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. The International HapMap Consortium. International HapMap Project. Nature 2003; 426: 789–796.

  20. Hugot JP, Laurent-Puig P, Gower-Rousseau C et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature 1996; 379: 821–823.

    CAS  PubMed  Google Scholar 

  21. Satsangi J, Parkes M, Louis E 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.

    CAS  PubMed  Google Scholar 

  22. Cho JH, Nicolae DL, Gold LH et al. 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 USA 1998; 95: 7502–7507.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Hampe J, Schreiber S, Shaw SH et al. A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort. Am J Hum Genet 1999; 64: 808–816.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ma Y, Ohmen JD, Li Z et al. A genome wide search identifies potential new susceptibility loci for Crohn's disease. Inflamm Bowel Dis 1999; 5: 271–278.

    CAS  PubMed  Google Scholar 

  25. Duerr RH, Barmada MM, Zhang L et al. High-Density Genome Scan in Crohn disease Shows Confirmed Linkage to Chromosome 14q11-12. Am J Hum Genet 2000; 66: 1857–1862.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Williams CN, Kocher K, Lander ES, Daly MJ, Rioux JD . Using a genome-wide scan and meta-analysis to identify a novel IBD locus and confirm previously identified IBD loci. Inflamm Bowel Dis 2002; 8: 375–381.

    PubMed  Google Scholar 

  28. Paavola-Sakki P, Ollikainen V, Helio T et al. Genome-wide search in Finnish families with inflammatory bowel disease provides evidence for novel susceptibility loci. Eur J Hum Genet 2003; 11: 112–120.

    CAS  PubMed  Google Scholar 

  29. Vermeire S, Rutgeerts P, Van Steen K et al. Genome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis. Gut 2004; 53: 980–986.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Barmada MM, Brant SR, Nicolae DL et al. A genome scan in 260 inflammatory bowel disease-affected relative pairs. Inflamm Bowel Dis 2004; 10: 15–22.

    PubMed  Google Scholar 

  31. van Heel DA, Fisher SA, Kirby A, Daly MJ, Rioux JD, Lewis CM . Genome Scan Meta-Analysis Group of the IBD International Genetics Consortium Inflammatory bowel disease susceptibility loci defined by genome scan meta-analysis of 1952 affected relative pairs. Hum Mol Genet 2004; 13: 763–770.

    CAS  PubMed  Google Scholar 

  32. Hugot JP, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001; 411: 599–603.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  35. Lesage S, Zouali H, Cezard JP et al. CARD15/NOD2 mutational analysis and genotype–phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet 2002; 70: 845–857.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Rosenstiel P, Fantini M, Brautigam K et al. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology 2003; 124: 1001–1009.

    CAS  PubMed  Google Scholar 

  37. Lala S, Ogura Y, Osborne C et al. Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology 2003; 125: 47–57.

    CAS  PubMed  Google Scholar 

  38. Hisamatsu T, Suzuki M, Reinecker HC, Nadeau WJ, McCormick BA, Podolsky DK . CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology 2003; 124: 993–1000.

    CAS  PubMed  Google Scholar 

  39. Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G . Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 2001; 276: 4812–4818.

    CAS  PubMed  Google Scholar 

  40. Gutierrez O, Pipaon C, Inohara N et al. Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. J Biol Chem 2002; 277: 41701–41705.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  43. Wehkamp J, Harder J, Weichenthal M et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 2004; 53: 1658–1664.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Watanabe T, Kitani A, Murray PJ, Strober W . NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 2004; 5: 800–808.

    CAS  PubMed  Google Scholar 

  45. Maeda S, Hsu LC, Liu H et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science 2005; 307: 734–738.

    CAS  PubMed  Google Scholar 

  46. Stoll M, Corneliussen B, Costello CM et al. Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 2004; 36: 476–480.

    CAS  PubMed  Google Scholar 

  47. Daly MJ, Pearce AV, Farwell L et al. Association of DLG5 R30Q variant with inflammatory bowel disease. Eur J Hum Genet 2005; 13: 835–839.

    CAS  PubMed  Google Scholar 

  48. Noble CL, Nimmo ER, Drummond H et al. DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population. Gut 2005; Apr 20 (Epub ahead of print).

  49. Torok HP, Glas J, Tonenchi L et al. Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease. Gut 2005; Jun 14 (Epub ahead of print).

  50. Vermeire S, Pierik M, Henckaerts L et al. Study on DLG5 and OCTN polymorphisms shows association of the OCTN TC risk haplotype with perianal and fistulizing Crohn's disease but not with susceptibility to IBD. Gastroenterol, in press.

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

    CAS  PubMed  Google Scholar 

  52. Rioux JD, Daly MJ, Silverberg MS et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet 2001; 29: 223–228.

    CAS  PubMed  Google Scholar 

  53. Giallourakis C, Stoll M, Miller K et al. IBD5 is a general risk Factor for inflammatory bowel disease: replication of association with Crohn's disease and identification of a novel association with ulcerative colitis? Am J Hum Genet 2003; 73: 205–211.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Negoro K, McGovern DPB, Kinouchi Y et al. Analysis of the IBD5 locus and potential gene–gene interactions in Crohn's disease. Gut 2003; 52: 541–546.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Mirza MM, Fisher SA, King K et al. Genetic evidence for interaction of the 5q31 cytokine locus and the CARD15 gene in Crohn disease. Am J Hum Genet 2003; 72: 1018–1022.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Mc Govern DPB, van Heel DA, Negoro K et al. Further evidence of IBD5/CARD15 (NOD2) epistasis in the susceptibility to ulcerative colitis. Am J Hum Genet 2003; 73: 1465–1466.

    CAS  Google Scholar 

  57. Gründemann D, Gorboulev V, Gambaryan S et al. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 1994; 372: 549–552.

    PubMed  Google Scholar 

  58. Lahjouji K, Mitchell GA, Qureshi IA . Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol Genet Metab 2001; 73: 287–297.

    CAS  PubMed  Google Scholar 

  59. Tamai I, Yabuuchi H, Nezu J et al. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett 1997; 419: 107–111.

    CAS  PubMed  Google Scholar 

  60. Wu X, Prasad PD, Leibach FH et al. cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun 1998; 246: 589–595.

    CAS  PubMed  Google Scholar 

  61. Roediger WE, Nance S . Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. Br J Exp 1986; 67: 773–782.

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  63. Zouali H, Lesage S, Merlin F et al. CARD4/NOD1 is not involved in inflammatory bowel disease. Gut 2003; 52: 71–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Toyoda H, Wang SJ, Yang HY et al. Distinct associations of HLA class II genes with inflammatory bowel disease. Gastroenterology 1993; 104: 741–748.

    CAS  PubMed  Google Scholar 

  65. Danze PM, Colombel JF, Jacquot S et al. Association of HLA class II genes with susceptibility to Crohn's disease. Gut 1996; 39: 69–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Satsangi J, Welsh KI, Bunce M et al. Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet 1996; 347: 1212–1217.

    CAS  PubMed  Google Scholar 

  67. Stokkers PC, Reitsma PH, Tytgat GN et al. HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis. Gut 1999; 45: 395–401.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Franchimont D, Vermeire S, El Housni H et al. 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 2004; 53: 987–992.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Lakatos PL, Lakatos L, Szalay F et al, Hungarian IBD Study Group. Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: phenotype–genotype correlations. World J Gastroenterol 2005; 11: 1489–1495.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Gazouli M, Mantzaris G, Kotsinas A et al. Association between polymorphisms in the Toll-like receptor 4, CD14, and CARD15/NOD2 and inflammatory bowel disease in the Greek population. World J Gastroenterol 2005; 11: 681–685.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Torok HP, Glas J, Tonenchi L et al. Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. Clin Immunol 2004; 112: 85–91.

    CAS  PubMed  Google Scholar 

  72. Oostenbrug LE, Drenth JP, de Jong DJ et al. Association between Toll-like receptor 4 and inflammatory bowel disease. Inflamm Bowel Dis 2005; 11: 567–575.

    PubMed  Google Scholar 

  73. Abreu MT, Taylor KD, Lin YC et al. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. Gastroenterology 2002; 123: 679–688.

    CAS  PubMed  Google Scholar 

  74. Ahmad T, Armuzzi A, Bunce M et al. The molecular classification of the clinical manifestations of Crohn's disease. Gastroenterology 2002; 122: 854–866.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  76. Cuthbert AP, Fisher SA, Mirza MM et al. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology 2002; 122: 867–874.

    CAS  PubMed  Google Scholar 

  77. Esters N, Pierik M, van Steen K et al. Transmission of CARD15 (NOD2) variants within families of patients with inflammatory bowel disease. Am J Gastroenterol 2004; 99: 299–305.

    CAS  PubMed  Google Scholar 

  78. Mendoza JL, Murillo LS, Fernandez L 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: 1235–1240.

    CAS  PubMed  Google Scholar 

  79. Roussomoustakaki M, Koutroubakis I, Vardas EM et al. NOD2 insertion mutation in a Cretan Crohn's disease population. Gastroenterology 2003; 124: 272–273.

    PubMed  Google Scholar 

  80. Vermeire S, Wild G, Kocher K et al. CARD15 genetic variation in a Quebec population: prevalence, genotype–phenotype relationship, and haplotype structure. Am J Hum Genet 2002; 71: 74–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Helio T, Halme L, Lappalainen M et al. CARD15/NOD2 gene variants are associated with familially occurring and complicated forms of Crohn's disease. Gut 2003; 52: 558–562.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Bairead E, Harmon DL, Curtis AM et al. Association of NOD2 with Crohn's disease in a homogenous Irish population. Eur J Hum Genet 2003; 11: 237–244.

    CAS  PubMed  Google Scholar 

  83. Arnott ID, Nimmo ER, Drummond HE et al. NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe? Genes Immun 2004; 5: 417–425.

    CAS  PubMed  Google Scholar 

  84. Inoue N, Tamura K, Kinouchi Y et al. Lack of common NOD2 variants in Japanese patients with Crohn's disease. Gastroenterology 2002; 123: 86–91.

    CAS  PubMed  Google Scholar 

  85. Sugimura M, Kinouchi Y, Takahashi S et al. CARD15/NOD2 mutational analysis in Japanese patients with Crohn's disease. Clin Genet 2003; 63: 160–162.

    CAS  PubMed  Google Scholar 

  86. Leong RWL, Armuzzi A, Ahmad T et al. NOD2/CARD15 gene polymorphisms and Crohn's disease in the Chinese population. Aliment Pharmacol Ther 2003; 17: 1465–1470.

    CAS  PubMed  Google Scholar 

  87. Bonen DK, Niclolae DL, Moran T et al. Racial differences in Nod2 variation: characterization of Nod2 in African-Americans with Crohn ‘s disease. Gastroenterology 2002; 122 (Suppl): A-29.

    Google Scholar 

  88. Hampe J, Grebe J, Nikolaus S et al. Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a Cohort Study. Lancet 2002; 359: 1661–1665.

    CAS  PubMed  Google Scholar 

  89. Holler E, Rogler G, Herfarth H et al. Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood 2004; 104: 889–894.

    CAS  PubMed  Google Scholar 

  90. Armuzzi A, Ahmad T, Ling KL et al. Genotype–phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31. Gut 2003; 52: 1133–1139.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Libioulle C, Thys J, Farnir F et al. Functional variants of Octn cation transporter gene are associated with perianal Crohn's disease. Gastroenterol Suppl 2005; 128: A445.

    Google Scholar 

  92. Newman B, Gu X, Wintle R et al. A risk haplotype in the solute carrier family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease. Gastroenterology 2005; 128: 260–269.

    CAS  PubMed  Google Scholar 

  93. Roussomoustakaki M, Satsangi J, Welsh K et al. Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology 1997; 112: 1845–1853.

    CAS  PubMed  Google Scholar 

  94. Orchard TR, Thiyagaraja S, Welsh KI et al. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 2000; 118: 274–278.

    CAS  PubMed  Google Scholar 

  95. Orchard TR, Chua CN, Ahmad T et al. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology 2002; 123: 714–718.

    PubMed  Google Scholar 

  96. Orchard TR, Wordsworth BP, Jewell DP . Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history. Gut 1998; 42: 387–391.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Hoffmeyer S, Burk O, von Richter O et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000; 97: 3473–3478.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Farrell RJ, Murphy A, Long A et al. High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy. Gastroenterology 2000; 118: 279–288.

    CAS  PubMed  Google Scholar 

  99. Honda M, Orii F, Ayabe T et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis. Gastroenterology 2000; 118: 859–866.

    CAS  PubMed  Google Scholar 

  100. Weinshilboum RM, Sladek SL . Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32: 651–662.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Yates CR, Krynetski EY, Loennechen T et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 1997; 126: 608–614.

    CAS  PubMed  Google Scholar 

  102. Dubinsky MC, Lamothe S, Yang HY et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118: 705–713.

    CAS  PubMed  Google Scholar 

  103. Cuffari C, Hunt S, Bayless T . Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease. Gut 2001; 48: 642–646.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Colombel JF, Ferrari N, Debuysere H et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000; 118: 1025–1030.

    CAS  PubMed  Google Scholar 

  105. Dubinsky MC, Yang H, Hassard PV et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002; 122: 904–915.

    CAS  PubMed  Google Scholar 

  106. Louis E, Vermeire S, Rutgeerts P et al. A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with −308 TNF gene polymorphism. Scand J Gastroenterol 2002; 37: 818–824.

    CAS  PubMed  Google Scholar 

  107. Mascheretti S, Hampe J, Kuhbacher T et al. Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn's disease treated with infliximab. Pharmacogenom J 2002; 2: 127–136.

    CAS  Google Scholar 

  108. Pierik M, Vermeire S, Van Steen K et al. TNF-Alpha receptor 1 and 2 (TNFR1 and TNFR2) polymorphisms in IBD and their association with response to infliximab. Aliment Pharmacol Ther 2004; 20: 303–310.

    CAS  PubMed  Google Scholar 

  109. Vermeire S, Louis E, Rutgeerts P et al Belgian Group of Infliximab Expanded Access Program and Fondation Jean Dausset CEPH, Paris, France. NOD2/CARD15 does not influence response to infliximab in Crohn's disease. Gastroenterology 2002; 123: 106–111.

    CAS  PubMed  Google Scholar 

  110. Mascheretti S, Hampe J, Croucher PJ et al. 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; 12: 509–515.

    CAS  PubMed  Google Scholar 

  111. Louis E, El Ghoul Z, Vermeire S et al. Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease. Aliment Pharmacol Ther 2004; 19: 511–519.

    CAS  PubMed  Google Scholar 

  112. Weng WK, Levy R . Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 2003; 21: 3940–3947.

    CAS  PubMed  Google Scholar 

  113. Cartron G, Dacheux L, Salles G et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 2002; 99: 754–758.

    CAS  PubMed  Google Scholar 

  114. Hlavaty T, Pierik M, Joossens S et al. Genotype TT in the promoter region of apoptotic gene Fas ligand is associated with unfavorable clinical response to infliximab treatment in refractory luminal Crohn's disease. Aliment Pharmacol Ther (in press).

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology - Herestraat, University Hospital Gasthuisberg Leuven, Leuven, Belgium

    S Vermeire & P Rutgeerts

Authors
  1. S Vermeire
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Rutgeerts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Vermeire.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vermeire, S., Rutgeerts, P. Current status of genetics research in inflammatory bowel disease. Genes Immun 6, 637–645 (2005). https://doi.org/10.1038/sj.gene.6364257

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364257

Keywords

This article is cited by

Search

Advanced search

Quick links