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

171 Citations (Scopus)

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 2003

Fingerprint

Tobacco Use
Ileal Diseases
Age of Onset
Phenotype
Mutation
Crohn Disease
Genes
Smoking
History
Genotype
Odds Ratio
Survival

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Chron's disease phenotypes. / Brant, Steven R.; Picco, Michael F.; Achkar, Jean Paul; Bayless, Theodore M.; Kane, Sunanda V.; Brzezinski, Aaron; Nouvet, Franklin J.; Bonen, Denise; Karban, Amir; Dassopoulos, Themistocles; Karaliukas, Reda; Beaty, Terri H.; Hanauer, Stephen B.; Duerr, Richard H.; Cho, Judy H.

In: Inflammatory Bowel Diseases, Vol. 9, No. 5, 09.2003, p. 281-289.

Research output: Contribution to journalArticle

Brant, SR, Picco, MF, Achkar, JP, Bayless, TM, Kane, SV, Brzezinski, A, Nouvet, FJ, Bonen, D, Karban, A, Dassopoulos, T, Karaliukas, R, Beaty, TH, Hanauer, SB, Duerr, RH & Cho, JH 2003, 'Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Chron's disease phenotypes', Inflammatory Bowel Diseases, vol. 9, no. 5, pp. 281-289. https://doi.org/10.1097/00054725-200309000-00001
Brant, Steven R. ; Picco, Michael F. ; Achkar, Jean Paul ; Bayless, Theodore M. ; Kane, Sunanda V. ; Brzezinski, Aaron ; Nouvet, Franklin J. ; Bonen, Denise ; Karban, Amir ; Dassopoulos, Themistocles ; Karaliukas, Reda ; Beaty, Terri H. ; Hanauer, Stephen B. ; Duerr, Richard H. ; Cho, Judy H. / Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Chron's disease phenotypes. In: Inflammatory Bowel Diseases. 2003 ; Vol. 9, No. 5. pp. 281-289.
@article{7596f9e5454645e4993fb63d21099419,
title = "Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Chron'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.",
keywords = "Crohn's disease, Fistula, Ileum, NOD2, Smoking, Stricture",
author = "Brant, {Steven R.} and Picco, {Michael F.} and Achkar, {Jean Paul} and Bayless, {Theodore M.} and Kane, {Sunanda V.} and Aaron Brzezinski and Nouvet, {Franklin J.} and Denise Bonen and Amir Karban and Themistocles Dassopoulos and Reda Karaliukas and Beaty, {Terri H.} and Hanauer, {Stephen B.} and Duerr, {Richard H.} and Cho, {Judy H.}",
year = "2003",
month = "9",
doi = "10.1097/00054725-200309000-00001",
language = "English (US)",
volume = "9",
pages = "281--289",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Chron's disease phenotypes

AU - Brant, Steven R.

AU - Picco, Michael F.

AU - Achkar, Jean Paul

AU - Bayless, Theodore M.

AU - Kane, Sunanda V.

AU - Brzezinski, Aaron

AU - Nouvet, Franklin J.

AU - Bonen, Denise

AU - Karban, Amir

AU - Dassopoulos, Themistocles

AU - Karaliukas, Reda

AU - Beaty, Terri H.

AU - Hanauer, Stephen B.

AU - Duerr, Richard H.

AU - Cho, Judy H.

PY - 2003/9

Y1 - 2003/9

N2 - 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.

AB - 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.

KW - Crohn's disease

KW - Fistula

KW - Ileum

KW - NOD2

KW - Smoking

KW - Stricture

UR - http://www.scopus.com/inward/record.url?scp=10744230291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744230291&partnerID=8YFLogxK

U2 - 10.1097/00054725-200309000-00001

DO - 10.1097/00054725-200309000-00001

M3 - Article

VL - 9

SP - 281

EP - 289

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 5

ER -