Genotype-based phenotyping heralds a new taxonomy for inflammatory bowel disease

Current Opinion in Gastroenterology

Volumn 19, Issue 4, 2003, Pages 327-335

  Ahmad, Tariq ^a   Marshall, Sara ^b   Jewell, Derek ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b ST MARY S HOSPITAL   (United Kingdom)

Author keywords

Classification; Genetics; Inflammatory bowel diseases; Phenotype

Indexed keywords

ANTIBIOTIC AGENT; AZATHIOPRINE; INFLIXIMAB; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; MULTIDRUG RESISTANCE PROTEIN 1; TUMOR NECROSIS FACTOR ALPHA;

ACCURACY; BONE MARROW SUPPRESSION; CARD15 GENE; CLINICAL FEATURE; COLON CROHN DISEASE; CROHN DISEASE; DISEASE CLASSIFICATION; DISEASE SEVERITY; DNA MODIFICATION; DRUG RESPONSE; ENTERITIS; ENVIRONMENTAL FACTOR; EPIDEMIOLOGICAL DATA; GENE; GENE IDENTIFICATION; GENE INTERACTION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENE MUTATION; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC MODEL; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; GENETICS; GENOTYPE ENVIRONMENT INTERACTION; GENOTYPE PHENOTYPE CORRELATION; HEREDITY; HLA SYSTEM; HUMAN; IBD5 GENE; LINKAGE ANALYSIS; NOD2 GENE; ONSET AGE; PREDICTION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TAXONOMY; ULCERATIVE COLITIS;

EID: 0037999892     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001574-200307000-00002     Document Type: Review

References (104)

1. Lewis T: Reflections upon reform in medical education. Lancet 1944, 1:619-621.
2. Bell J: The new genetics in clinical practice. BMJ 1998, 316:618-620.
3. Lockhart-Mummery HE, Morson BC: Crohn's disease (regional enteritis) of the large intestine and its distinction from ulcerative colitis. Gut 1960, 1:87-105.
4. Farmer RG, Hawk WA, Tumbull RB, Jr.: Clinical patterns in Crohn's disease: a statistical study of 615 cases. Gastroenterology 1975, 68:627-635.
5. Franchimont DP, Louis E, Croes F, Belaiche J: Clinical pattern of corticosteroid dependent Crohn's disease. Eur J Gastroenterol Hepatol 1998, 10:821-825.
6. Farmer RG, Whelan G, Fazio VW: Long-term follow-up of patients with Crohn's disease. Relationship between the clinical pattern and prognosis. Gastroenterology 1985, 88:1818-1825.
7. Whelan G, Farmer RG, Fazio VW, Goormastic M: Recurrence after surgery in Crohn's disease. Relationship to location of disease (clinical pattern) and surgical indication. Gastroenterology 1985, 88:1826-1833.
8. Griffiths AM, Wesson DE, Shandling B, Corey M, Sherman PM: Factors influencing postoperative recurrence of Crohn's disease in childhood. Gut 1991, 32:491-495.
9. Greenstein AJ, Lachman P, Sachar DB, Springhorn J, Heimann T, Janowitz HD, Aufses AH, Jr.: Perforating and non-perforating indications for repeated operations in Crohn's disease: evidence for two clinical forms. Gut 1988, 29:588-592.
10. Aeberhard P, Berchtold W, Reidtmann HJ, Stadelmann G: Surgical recurrence of perforating and nonperforating Crohn's disease. A study of 101 surgically treated Patients. Dis Colon Rectum 1996, 39:80-87.
11. Sachar DB, Andrews HA, Farmer RG, et al.: Proposed classification of patient subgroups in Crohn's disease. Gastroenterol Int 1992, 5:141-154.
12. Gasche C, Scholmerich J, Brynskov J, et al.: A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 2000, 6:8-15.
13. Vasiliauskas EA, Plevy SE, Landers CJ, et al.: Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup. Gastroenterology 1996, 110:1810-1819.
14. Vasiliauskas EA, Kam LY, Karp LC, et al.: Marker antibody expression stratifies Crohn's disease into immunologically homogeneous subgroups with distinct clinical characteristics. Gut 2000, 47:487-496.
15. Halme L, Turunen U, Helio T, et al.: Familial and sporadic inflammatory bowel disease: comparison of clinical features and serological markers in a genetically homogeneous population. Scand J Gastroenterol 2002, 37:692-698.
16. Achkar JP, Barmada MM, Duerr RH: Perinuclear neutrophil antibodies are not markers for genetic susceptibility or indicators of genetic heterogeneity in familial ulcerative colitis. Am J Gastroenterol 2002, 97:2343-2349.
17. Polito JM 2nd, Childs B, Mellits ED, et al.: Crohn's disease: influence of age at diagnosis on site and clinical type of disease. Gastroenterology 1996, 111:580-586.
18. Satsangi J, Grootscholten C, Holt H, et al.: Clinical patterns of familial inflammatory bowel disease. Gut 1996, 38:738-741.
19. Bayless TM, Tokayer AZ, Polito JM 2nd, et al.: Crohn's disease: concordance for site and clinical type in affected family members-potential hereditary influences. Gastroenterology 1996, 111:573-579.
20. Colombel JF, Grandbastien B, Gower-Rousseau C, et al.: Clinical characteristics of Crohn's disease in 72 families. Gastroenterology 1996, 111:604-607.
21. 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.
22. Annese V, Andreoli A, Astegiano M, et al.: Clinical features in familial cases of Crohn's disease and ulcerative colitis in Italy: a GISC study. Italian Study Group for the Disease of Colon and Rectum. Am J Gastroenterol 2001, 96:2939-2945.
23. Lander E, Kruglyak L: Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995, 11:241-247.
24. 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.
25. 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.
26. Ohmen JD, Yang HY, Yamamoto KK, et al.: 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, 5:1679-1683.
27. 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 U S A 1998, 95:7502-7507.
28. Brant SR, Fu Y, Fields CT, et al.: American families with Crohn's disease have strong evidence for linkage to chromosome 16 but not chromosome 12. Gastroenterology 1998, 115:1056-1061.
29. Curran ME, Lau KF, Hampe J, et al.: Genetic analysis of inflammatory bowel disease in a large European cohort supports linkage to chromosomes 12 and 16. Gastroenterology 1998, 115:1066-1071.
30. Cavanaugh JA, Callen DF, Wilson SR, et al.: Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16. Ann Hum Genet 1998, 62(Pt 4):291-298.
31. 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.
32. Annese V, Latiano A, Bovio P, et al.: Genetic analysis in Italian families with inflammatory bowel disease supports linkage to the IBD1 locus: a GISC study. Eur J Hum Genet 1999, 7:567-573.
33. Cavanaugh J: 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, 68:1165-1171.
34. Duerr RH, Barmada MM, Zhang L, et al.: Linkage and association between inflammatory bowel disease and a locus on chromosome 12. Am J Hum Genet 1998, 63:95-100.
35. 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.
36. Yang H, Plevy SE, Taylor K, et al.: Linkage of Crohn's disease to the major histocompatibility complex region is detected by multiple non-parametric analyses. Gut 1999, 44:519-526.
37. Hampe J, Shaw SH, Saiz R, et al.: Linkage of inflammatory bowel disease to human chromosome 6p. Am J Hum Genet 1999, 65:1647-1655.
38. Rioux JD, Silverberg MS, Daly MJ, et al.: Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet 2000, 66:1863-1870.
39. Dechairo B, Dimon C, van Heel D, et al.: Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3). Eur J Hum Genet 2001, 9:627-633.
40. 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.
41. Hampe J, Lynch NJ, Daniels S, et al.: Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease. Gut 2001, 48:191-197.
42. Paavola P, Helio T, Kiuru M, et al.: Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21. Eur J Hum Genet 2001, 9:328-334.
43. Duerr RH, Barmada MM, Zhang L, et al.: Evidence for an inflammatory bowel disease locus on chromosome 3p26: linkage, transmission/disequilibrium and partitioning of linkage. Hum Mol Genet 2002, 11:2599-2606. This study illustrates the greater power of allelic association-based methods compared with linkage analyses to detect disease loci with only modest effects. Reanalysis of geneme scan data using a transmission/disequilibrium test identified a locus on chromosome 3p26, to which only modest linkage had previously been demonstrated. Evidence of linkage to this locus in both UC and CD was then confirmed in a second independent cohort.
44. Cho JH, Nicolae DL, Ramos R, et al.: Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease. Hum Mol Genet 2000, 9:1425-1432.
45. Nadeau JH: Modifier genes in mice and humans. Nat Rev Genet 2001, 2:165-174.
46. Bridger S, Lee JC, Bjarnason I, et al.: In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis. Gut 2002, 51:21-25. This study confirms the positive association between smoking and ileal CD and negative association with UC and colonic CD. Interestingly in 21 sibpairs discordant for both IBD type and smoking history smokers developed CD and non-smokers UC. These data suggest that disease phenotype, in genetically susceptible individuals, may be influenced by environmental modifying factors.
47. Silverberg MS, Daly MJ, Moskovitz DN, et al.: Diagnostic misclassification reduces the ability to detect linkage in inflammatory bowel disease genetic studies. Gut 2001, 49:773-776.
48. Steinhart AH, Girgrah N, McLeod RS: Reliability of a Crohn's disease clinical classification scheme based on disease behavior. Inflamm Bowel Dis 1998, 4:228-234.
49. Louis E, Collard A, Oger AF, et al.: Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease. Gut 2001, 49:777-782.
50. Powell-Tuck J, Ritchie JK, Lennard-Jones JE: The prognosis of idiopathic proctitis. Scand J Gastroenterol 1977, 12:727-732.
51. Moum B, Ekbom A, Vatn MH, et al.: Change in the extent of colonoscopic and histological involvement in ulcerative colitis over time. Am J Gastroenterol 1999, 94:1564-1569.
52. Cardon LR, Bell JI: Association study designs for complex diseases. Nat Rev Genet 2001, 2:91-99.
53. Tabor HK, Risch NJ, Myers RM: Opinion: Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 2002, 3:391-397.
54. Ioannidis JP, Ntzani EE, Trikalinos TA, et al.: Replication validity of genetic association studies. Nat Genet 2001, 29:306-309.
55. Parkes M, Barmada MM, Satsangi J, et al.: The IBD2 locus shows linkage heterogeneity between ulcerative colitis and Crohn disease. Am J Hum Genet 2000, 67:1605-1610.
56. 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.
57. 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.
58. 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.
59. 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. The most comprehensive report published to date of nucleotide variation in the NOD2/CARD15 gene. This useful reference paper details an additional 27 rare possible disease causing mutations identified from screening 453 CD patients.
60. Vavassori P, Borgiani P, D'Apice MR, et al.: 3020insC mutation within the NOD2 gene in Crohn's disease: frequency and association with clinical pattern in an Italian population. Dig Liver Dis 2002, 34:153.
61. Ahmad T, Armuzzi A, Bunce M, et al.: The molecular classification of the clinical manifestations of Crohn's disease. Gastroenterology 2002, 122:854-866. In this genotype-phenotype analysis emphasis is placed upon careful clinical phenotyping of disease. In this single centre study NOD2/CARD 15 variant alleles are shown to be associated with colonic and perianal CD. Genetic heterogeneity is demonstrated between the HLA and NOD2/CARD15.
62. 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. A large multicentre European study demonstrating association with 3 NOD2/CARD15 variant alleles using both case control and TDT analyses. Genotype-phenotype analyses is presented for a subset of British patients.
63. Murillo L, Crusius JB, van Bodegraven AA, et al.: CARD15 gene and the classification of Crohn's disease. Immunogenetics 2002, 54:59-61.
64. 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.
65. Radlmayr M, Torok HP, Martin K, et al.: The c-insertion mutation of the NOD2 gene is associated with fistulizing and fibrostenotic phenotypes in Crohn's disease. Gastroenterology 2002, 122:2091-2092.
66. 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. This genotype-phenotype study additionally investigates possible epistasis between NOD2/CARD15 and IBD5 and also examines the haplotype structure in a region surrounding the NOD2/CARD15 gene, in an attempt to clarify the history of the causal mutations.
67. 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. This group has previously reported an association between fibrostenosing disease and the serum marker ASCA. In this two-stage genotype-phenotype study from a single centre NOD2 variant alleles are shown to be associated with fibrostenosing disease but not ASCA positivity.
68. Van Heel DA, McGovern DP, Cardon LR, et al.: Fine mapping of the IBD1 locus did not identify Crohn disease-associated NOD2 variants: Implications for complex disease genetics. Am J Med Genet 2002, 111:253-259. This study illustrates the difficulties facing microsatellite linkage and linkage disequilibrium mapping strategies used for identifying genes in complex traits. Despite significant association with 2 NOD2/CARD15 variant alleles no evidence for linkage or association was found for microsatellite markers surrounding the NOD2/CARD15 gene.
69. Zhou Z, Lin XY, Akolkar PN, et al.: Variation at NOD2/CARD15 in familial and sporadic cases of Crohn's disease in the Ashkenazi Jewish population. Am J Gastroenterol 2002, 97:3095-3101. Data from this study, of exclusively Jewish patients, suggests that the relative importance of specific NOD2/CARD15 variants may be different in Jewish patients.
70. Orholm M, Iselius L, Sorensen TI, et al.: Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis. BMJ 1993, 306:20-24.
71. Forabosco P, Collins A, Latiano A, et al.: Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis. On behalf of the GISC. Eur J Hum Genet 2000, 8:846-852.
72. 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. There is more than one molecular route to the same phenotype. This genetic heterogeneity is illustrated by the fact that NOD2/CARD15 is polymorphisms have not been identified in Japanese patients with Crohn's disease
73. Yamazaki K, Takazoe M, Tanaka T, et al.: Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with Crohn's disease. J Hum Genet 2002, 47:469-472. See comment on Reference 72.
74. van der Linde K, Boor PP, Houwing-Duistermaat JJ, et al.: CARD15 and Crohn's Disease: Healthy homozygous carriers of 30206 frameshift mutation. Am J Gastro 2003, 98(3):613-617.
75. Negoro K, McGovern D, Kinouchi Y, et al.: Role of the 5q31 cytokine gene cluster haplotype (IBD5) in Japanese and British inflammatory bowel disease: evidence for genetic heterogeneity. Gastroenterology 2002, 122:A30.
76. Vijgen L, Van Gysel M, Rector A, et al.: Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease. Genes Immun 2002, 3:400-406.
77. Cottone M, Brignola C, Rosselli M, et al.: Relationship between site of disease and familial occurrence in Crohn's disease. Dig Dis Sci 1997, 42:129-132.
78. 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.
79. Armuzzi A, Ahmad T, Ling K-L, et al.: Genotype-phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31. Gastroenterology in press.
80. Aithal GP, Day CP, Leathart J, et al.: Association of single nucleotide polymorphisms in the interleukin-4 gene and interleukin-4 receptor gene with Crohn's disease in a British population. Genes Immun 2001, 2:44-47.
81. Klein W, Tromm A, Griga T, et al.: The polymorphism at position-174 of the IL-6 gene is not associated with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2001, 13:45-47.
82. Obana N, Takahashi S, Kinouchi Y, et al.: Ulcerative colitis is associated with a promoter polymorphism of lipopolysaccharide receptor gene, CD14. Scand J Gastroenterol 2002, 37:699-704.
83. Klein W, Tromm A, Griga T, et al.: A polymorphism in the CD14 gene is associated with Crohn disease. Scand J Gastroenterol 2002, 37:189-191.
84. McGovern D, Negoro K, van Heel D, et al.: CD14 and PPAR polymorphisms: candidate genes for IBD? Gut 2002, 50:A73.
85. 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.
86. 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.
87. Trachtenberg EA, Yang H, Hayes E, et al.: HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish caucasian populations. Hum Immunol 2000, 61:326-333.
88. Silverberg M, Mirea L, Bull S, et al.: A population- and family-based study of Canadian families reveals association of HLA-DRB1*0103 with colonic involvement in inflammatory bowel disease. Inflamm Bowel Dis 2003, 9:1-9.
89. 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.
90. Roussomoustakaki M, Satsangi J, Welsh K, et al.: Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology 1997, 112:1845-1853.
91. 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.
92. Ahmad T, Armuzzi A, Bunce M, et al.: Role of the HLA in determining susceptibitity and phenotype in Caucasian ulcerative colitis. Gastroenterology 2002, 122:A302.
93. Yamamoto-Furusho JK, Uscanga LF, Vargas-Alarcon G, et al.: Clinical and genetic heterogeneity in Mexican patients with ulcerative colitis. Hum Immunol 2003, 64:119-123.
94. Louis E, Peeters M, Franchimont D, et al.: Tumour necrosis factor (TNF) gene polymorphism in Crohn's disease (CD): influence on disease behaviour? Clin Exp Immunol 2000, 119:64-68.
95. 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.
96. 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.
97. Craggs A, West S, Curtis A, et al.: Absence of a genetic association between IL-1RN and IL-1B gene polymorphisms in ulcerative colitis and Crohn disease in multiple populations from northeast England. Scand J Gastroenterol 2001, 36:1173-1178.
98. Carter MJ, di Giovine FS, Jones S, et al.: Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in northern European Caucasians. Gut 2001, 48:461-467.
99. Carter MJ, Di Giovine FS, Cox A, et al.: The interleukin 1 receptor antagonist gene allele 2 as a predictor of pouchitis following colectomy and IPAA in ulcerative colitis. Gastroenterology 2001, 121:805-811.
100. Schwab M, Schaeffeler E, Marx C, et al.: Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis. Gastroenterology 2003, 124:26-33. An association study of a functionally significant polymorphism in a plausible positional and functional candidate gene, which importantly is supported by a mouse knockout model of disease.
101. McGovern D, van Heel D, Ahmad T, et al.: Cytochrome P450 and multidrug-resistance gene polymorphisms: predictors of the need for colectomy in ulcerative colitis? Gut 2002, 50:A74.
102. Taylor KD, Plevy SE, Yang H, et al.: ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease. Gastroenterology 2001, 120:1347-1355.
103. 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.
104. Vermeire S, Louis E, Rutgeerts P, et al.: NOD2/CARD15 does not influence response to infliximab in Crohn's disease. Gastroenterology 2002, 123:106-111.