Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn's disease phenotypes
Corresponding Author
Dr. Steven R. Brant
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Room B136, Baltimore, MD 21231-1001, U.S.A.Search for more papers by this authorMichael F. Picco
Department of Gastroenterology, Mayo Clinic, Jacksonville, Florida, U.S.A.
Search for more papers by this authorJean-Paul Achkar
Department of Gastroenterology, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.
Search for more papers by this authorTheodore M. Bayless
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorSunanda V. Kane
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorAaron Brzezinski
Department of Genetic Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, U.S.A.
Search for more papers by this authorFranklin J. Nouvet
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorDenise Bonen
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorAmir Karban
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorThemistocles Dassopoulos
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorReda Karaliukas
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorTerri H. Beaty
Department of Genetic Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, U.S.A.
Search for more papers by this authorStephen B. Hanauer
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorRichard H. Duerr
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, and Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
Search for more papers by this authorJudy H. Cho
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorCorresponding Author
Dr. Steven R. Brant
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Room B136, Baltimore, MD 21231-1001, U.S.A.Search for more papers by this authorMichael F. Picco
Department of Gastroenterology, Mayo Clinic, Jacksonville, Florida, U.S.A.
Search for more papers by this authorJean-Paul Achkar
Department of Gastroenterology, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.
Search for more papers by this authorTheodore M. Bayless
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorSunanda V. Kane
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorAaron Brzezinski
Department of Genetic Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, U.S.A.
Search for more papers by this authorFranklin J. Nouvet
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorDenise Bonen
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorAmir Karban
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorThemistocles Dassopoulos
The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Dept. of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Search for more papers by this authorReda Karaliukas
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorTerri H. Beaty
Department of Genetic Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, U.S.A.
Search for more papers by this authorStephen B. Hanauer
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorRichard H. Duerr
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, and Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
Search for more papers by this authorJudy H. Cho
The Martin Boyer Genetics Research Laboratories, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois, U.S.A.
Search for more papers by this authorAbstract
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.
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