Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Chron's disease phenotypes

Steven R. Brant, Michael F. Picco, Jean Paul Achkar, Theodore M. Bayless, Sunanda V. Kane, Aaron Brzezinski, Franklin J. Nouvet, Denise Bonen, Amir Karban, Themistocles Dassopoulos, Reda Karaliukas, Terri H. Beaty, Stephen B. Hanauer, Richard H. Duerr, Judy H. Cho

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

Background: Multiple factors, particularly IBD family history, tobacco use, age at diagnosis and recently, NOD2 mutant genotypes may influence Crohn's disease (CD) heterogeneity. Methods: We performed a multicenter retrospective record analysis of 275 unrelated patients with CD. Age at diagnosis, IBD family history, Jewish ethnicity, tobacco use at diagnosis, surgical history, disease site and clinical behavior were correlated with genotypes for NOD2 mutations, and all risk factors were assessed for independent influence on outcomes of disease site, behavior and surgery free survival. Results: Risk of ileal disease was increased for CD patients with two NOD2 mutations (Odds Ratio, O.R. 10.1), a smoking history (O.R. 2.25 per pack per day at diagnosis) or a younger age at diagnosis (O.R. 0.97 per each increased year). Presence of ileal disease (O.R. 4.8) and carrying one or two NOD2 mutations (O.R. 1.9 and 3.5, respectively) were independent risk factors for stricturing or non-perianal fistulizing behavior. Ileal disease, youthful onset and smoking at diagnosis (but not NOD2 mutations) were risk factors for early surgery. Conclusions: Carrying two NOD2 mutations predicts youthful onset, ileal disease involvement, and development of stricturing or non-perianal fistulizing complications. Smoking and early onset independently influence ileal site and time to surgery.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalInflammatory bowel diseases
Volume9
Issue number5
DOIs
StatePublished - Sep 1 2003

Keywords

  • Crohn's disease
  • Fistula
  • Ileum
  • NOD2
  • Smoking
  • Stricture

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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    Brant, S. R., Picco, M. F., Achkar, J. P., Bayless, T. M., Kane, S. V., Brzezinski, A., Nouvet, F. J., Bonen, D., Karban, A., Dassopoulos, T., Karaliukas, R., Beaty, T. H., Hanauer, S. B., Duerr, R. H., & Cho, J. H. (2003). Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Chron's disease phenotypes. Inflammatory bowel diseases, 9(5), 281-289. https://doi.org/10.1097/00054725-200309000-00001