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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 07 Mar 2003

Chamaillard M, Philpott D, Girardin SE, Zouali H, Lesage S, Chareyre F, Bui TH, Giovannini M, Zaehringer U, Penard-Lacronique V, Sansonetti PJ, Hugot JP, Thomas G

Link to Pubmed [PMID] – 12626759

Proc. Natl. Acad. Sci. U.S.A. 2003 Mar;100(6):3455-60

CARD15 is a major susceptibility gene for a frequent multifactorial chronic inflammatory bowel disorder, Crohn disease (CD). By using NF-kappaB activation assays, the cytosolic CARD15 was shown to efficiently detect bacterial peptidoglycan (PGN), reminiscent of the PGN recognition protein surveillance mechanism in Drosophila. The 3 CD-associated variants and 13 additional variants carried by CD patients demonstrated impaired PGN-dependent response revealing null, hypomorphic, or dominant-negative properties. Quantitative parametrization of this response, computed from the patients’ CARD15 genotypes, was predictive of several variable CD manifestations. In contrast, CARD15 alleles associated with Blau’s syndrome promoted PGN-independent NF-kappaB activation, an observation that accounts for the minimal microbial input in the etiology of this dominant, monogenic inflammatory disorder affecting solely aseptic sites.

http://www.ncbi.nlm.nih.gov/pubmed/12626759