RT Journal Article
SR Electronic
T1 CARD4/NOD1 is not involved in inflammatory bowel disease
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 71
OP 74
DO 10.1136/gut.52.1.71
VO 52
IS 1
A1 H Zouali
A1 S Lesage
A1 F Merlin
A1 J-P Cézard
A1 J-F Colombel
A1 J Belaiche
A1 S Almer
A1 C Tysk
A1 C O’Morain
A1 M Gassull
A1 S Christensen
A1 Y Finkel
A1 R Modigliani
A1 C Gower-Rousseau
A1 J Macry
A1 M Chamaillard
A1 G Thomas
A1 J-P Hugot
YR 2003
UL http://gut.bmj.com/content/52/1/71.abstract
AB 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.