The NOD2 p.Leu1007fsX1008 mutation (rs2066847) is a stronger predictor of the clinical course of Crohns disease than the FOXO3A Intron variant rs12212067

PLoS ONE

Volumn 9, Issue 11, 2014, Pages

  Schnitzler, Fabian ^a   Friedrich, Matthias ^a,b   Wolf, Christiane ^c   Angelberger, Marianne ^a   Diegelmann, Julia ^b   Olszak, Torsten ^a   Beigel, Florian ^a   Tillack, Cornelia ^a   Stallhofer, Johannes ^a   Göke, Burkhard ^a   Glas, Jürgen ^d   Lohse, Peter ^b,e   Brand, Stephan ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

^c MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^d RWTH AACHEN UNIVERSITY   (Germany)

^e Institute of Laboratory Medicine and Human Genetics   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ADALIMUMAB; AZATHIOPRINE; CASPASE RECRUITMENT DOMAIN PROTEIN 15; IMMUNOSUPPRESSIVE AGENT; INFLIXIMAB; MERCAPTOPURINE; METHOTREXATE; TRANSCRIPTION FACTOR FKHRL1; TUMOR NECROSIS FACTOR INHIBITOR; FORKHEAD TRANSCRIPTION FACTOR; FOXO3 PROTEIN, HUMAN;

ADOLESCENT; ADULT; AGE; AGED; ANUS FISTULA; ARTICLE; BODY MASS; CHILD; COLON RESECTION; CROHN DISEASE; DIGESTIVE SYSTEM FISTULA; DISEASE COURSE; DISEASE DURATION; DISEASE SEVERITY; FEMALE; FISTULECTOMY; FOXO3A GENE; FRAMESHIFT MUTATION; GASTROINTESTINAL SURGERY; GENE FREQUENCY; GENE MUTATION; GENOTYPE PHENOTYPE CORRELATION; HOMOZYGOSITY; HUMAN; ILEOCECAL RESECTION; ILEOSTOMY; ILEUM DISEASE; IMMUNOSUPPRESSIVE TREATMENT; INTESTINE STENOSIS; MAJOR CLINICAL STUDY; MALE; NOD2 GENE; PHENOTYPIC VARIATION; SINGLE NUCLEOTIDE POLYMORPHISM; ALLELE; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETICS; GENOTYPE; HOMOZYGOTE; INTRON; MIDDLE AGED; MUTATION; PHENOTYPE; PROGNOSIS; SEVERITY OF ILLNESS INDEX; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ALLELES; CHILD; CROHN DISEASE; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HOMOZYGOTE; HUMANS; INTRONS; MALE; MIDDLE AGED; MUTATION; NOD2 SIGNALING ADAPTOR PROTEIN; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROGNOSIS; SEVERITY OF ILLNESS INDEX; YOUNG ADULT;

EID: 84909594530     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0108503     Document Type: Article

References (31)

1. Billiet T, Rutgeerts P, Ferrante M, Van Assche G, Vermeire S (2014) Targeting TNF-alpha for the treatment of inflammatory bowel disease. Expert Opin Biol Ther 14: 75-101.
2. Brand S (2013) Moving the genetics of inflammatory bowel diseases from bench to bedside: first steps towards personalised medicine. Gut 62: 1531-1533.
3. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411: 599-603.
4. Seiderer J, Brand S, Herrmann KA, Schnitzler F, Hatz R, et al. (2006) Predictive value of the CARD15 variant 1007fs for the diagnosis of intestinal stenoses and the need for surgery in Crohn's disease in clinical practice: results of a prospective study. Inflamm Bowel Dis 12: 1114-1121.
5. Seiderer J, Schnitzler F, Brand S, Staudinger T, Pfennig S, et al. (2006) Homozygosity for the CARD15 frameshift mutation 1007fs is predictive of early onset of Crohn's disease with ileal stenosis, entero-enteral fistulas, and frequent need for surgical intervention with high risk of re-stenosis. Scand J Gastroenterol 41: 1421-1432.
6. Cleynen I, Gonzalez JR, Figueroa C, Franke A, McGovern D, et al. (2013) Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project. Gut 62: 1556-1565.
7. Adler J, Rangwalla SC, Dwamena BA, Higgins PD (2011) The prognostic power of the NOD2 genotype for complicated Crohn's disease: a meta-analysis. Am J Gastroenterol 106: 699-712.
8. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411: 603-606.
9. Schnitzler F, Seiderer J, Stallhofer J, Brand S (2012) Dominant disease-causing effect of NOD2 mutations in a family with all family members affected by Crohn's disease. Inflamm Bowel Dis 18: 395-396.
10. Brand S (2012) Homozygosity for the NOD2 p.Leu1007fsX1008 variant is the main genetic predictor for fibrostenotic Crohn's disease. Inflamm Bowel Dis 18: 393-394.
11. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, et al. (2012) Hostmicrobe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491: 119-124.
12. Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, et al. (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 42: 1118-1125.
13. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, et al. (2011) Metaanalysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43: 246-252.
14. Jurgens M, Brand S, Laubender RP, Seiderer J, Glas J, et al. (2010) The presence of fistulas and NOD2 homozygosity strongly predict intestinal stenosis in Crohn's disease independent of the IL23R genotype. J Gastroenterol 45: 721-731.
15. Lee JC, Espeli M, Anderson CA, Linterman MA, Pocock JM, et al. (2013) Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell 155: 57-69.
16. McKinney EF, Lyons PA, Carr EJ, Hollis JL, Jayne DR, et al. (2010) A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nat Med 16: 586-591, 581p following 591.
17. Lee JC, Lyons PA, McKinney EF, Sowerby JM, Carr EJ, et al. (2011) Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J Clin Invest 121: 4170-4179.
18. Accili D, Arden KC (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117: 421-426.
19. Burgering BM, Kops GJ (2002) Cell cycle and death control: long live Forkheads. Trends Biochem Sci 27: 352-360.
20. Modur V, Nagarajan R, Evers BM, Milbrandt J (2002) FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem 277: 47928-47937.
21. Nakae J, Oki M, Cao Y (2008) The FoxO transcription factors and metabolic regulation. FEBS Lett 582: 54-67.
22. Harada Y, Elly C, Ying G, Paik JH, DePinho RA, et al. (2010) Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. J Exp Med 207: 1381-1391.
23. Kerdiles YM, Stone EL, Beisner DR, McGargill MA, Ch'en IL, et al. (2010) Foxo transcription factors control regulatory T cell development and function. Immunity 33: 890-904.
24. Ouyang W, Beckett O, Ma Q, Paik JH, DePinho RA, et al. (2010) Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat Immunol 11: 618-627.
25. Glas J, Konrad A, Schmechel S, Dambacher J, Seiderer J, et al. (2008) The ATG16L1 gene variants rs2241879 and rs2241880 (T300A) are strongly associated with susceptibility to Crohn's disease in the German population. Am J Gastroenterol 103: 682-691.
26. Lennard-Jones JE (1989) Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl 170: 2-6; discussion 16-19.
27. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, et al. (2005) Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol19 Suppl A: 5A-36A.
28. Glas J, Seiderer J, Tillack C, Pfennig S, Beigel F, et al. (2010) The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants. PLoS One 5: e14466.
29. Glas J, Stallhofer J, Ripke S, Wetzke M, Pfennig S, et al. (2009) Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease. Am J Gastroenterol 104: 1737-1744.
30. Schnitzler F, Brand S, Staudinger T, Pfennig S, Hofbauer K, et al. (2006) Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease. Immunogenetics 58: 99-106.
31. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559-575.