title: Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn's disease phenotypes.
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.
authors.affiliation: The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, U.S.A. sbrant@mail.jhmi.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
authors.forename: Michael F
authors.initials: MF
authors.lastname: Picco
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Achkar
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Bayless
authors.forename: Sunanda V
authors.initials: SV
authors.lastname: Kane
authors.forename: Aaron
authors.initials: A
authors.lastname: Brzezinski
authors.forename: Franklin J
authors.initials: FJ
authors.lastname: Nouvet
authors.forename: Denise
authors.initials: D
authors.lastname: Bonen
authors.forename: Amir
authors.initials: A
authors.lastname: Karban
authors.forename: Themistocles
authors.initials: T
authors.lastname: Dassopoulos
authors.forename: Reda
authors.initials: R
authors.lastname: Karaliukas
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hanauer
authors.forename: Richard H
authors.initials: RH
authors.lastname: Duerr
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
mesh_terms: D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007077:Ileal Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D007585:Jews; D008297:Male; D053473:Nod2 Signaling Adaptor Protein; D016017:Odds Ratio; D010641:Phenotype; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein