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CARD4/NOD1 is not involved in inflammatory bowel disease
  1. H Zouali1,
  2. S Lesage1,
  3. F Merlin1,
  4. J-P Cézard2,
  5. The EPWG-IBD group2,
  6. J-F Colombel3,
  7. The EPIMAD group3,
  8. J Belaiche4,
  9. The GETAID Group4,
  10. S Almer5,
  11. C Tysk6,
  12. C O’Morain7,
  13. M Gassull8,
  14. S Christensen9,
  15. Y Finkel10,
  16. R Modigliani11,
  17. C Gower-Rousseau3,
  18. J Macry12,
  19. M Chamaillard1,
  20. G Thomas1,
  21. J-P Hugot13
  1. 1Fondation Jean Dausset-CEPH, Paris, France
  2. 2European Paediatric Working Group of the Genetics of IBD, Department of Paediatric Gastroenterology, Hôpital Robert Debré, Paris, France
  3. 3Registre EPIMAD, Service d’Épidémiologie et de Santé Publique, Hôpital Calmette, Lille, France
  4. 4Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Digestives, Department of Gastroenterology, CHU de Liége, Belgium
  5. 5Division of Gastroenterology and Hepatology, Institutionen för Molekylar och Klinisk Medicin, Linköpings Universitet, Linköping, Sweden
  6. 6Department of Gastroenterology, Örebro Medical Centre Hospital, Örebro, Sweden
  7. 7Department of Gastroenterology, Adelaide and Meath Hospital, Dublin, Ireland
  8. 8Department of Gastroenterology, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
  9. 9Department of Gastroenterology, Herlev Hospital, Herlev, Denmark
  10. 10Department of Gastroenterology, Karolinska Children’s Hospital, Stockholm, Sweden
  11. 11Department of Gastroenterology, Hôpital Saint Louis, Paris, France
  12. 12INSERM U458, Hôpital Robert Debré, Paris, France
  13. 13Fondation Jean Dausset-CEPH, Paris, France, and Department of Paediatric Gastroenterology, Hôpital Robert Debré, Paris, France
  1. Correspondence to:
    J-P Hugot, Fondation Jean Dausset, 27 rue Juliette Dodu, 75010 Paris, France; jean-pierre.hugot{at}cephb.fr

Abstract

Background and aims: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD.

Patients and methods: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test.

Results: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence.

Conclusion: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.

  • inflammatory bowel disease
  • Crohn’s disease
  • ulcerative colitis
  • CARD4/NOD1
  • linkage disequilibrium
  • IBD, inflammatory bowel disease
  • CD, Crohn’s disease
  • UC, ulcerative colitis
  • IC, indeterminate colitis
  • CARD4, caspase recruitment domain 4
  • TDT, transmission disequilibrium test. PCR, polymerase chain reaction
  • NBD, nucleotide binding domain
  • LRR, leucine rich repeats
  • LPS, lipopolysaccharide
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