Digestive Diseases and Sciences

, Volume 52, Issue 10, pp 2716–2724

CARD15 Genotype-Phenotype Relationships in a Small Inflammatory Bowel Disease Population with Severe Disease Affection Status

  • Nigel P. S. Crawford
  • Daniel W. Colliver
  • M. Robert Eichenberger
  • Alisa A. Funke
  • Valentina Kolodko
  • Gary A. Cobbs
  • Robert E. Petras
  • Susan Galandiuk
Original Paper

DOI: 10.1007/s10620-006-9208-z

Cite this article as:
Crawford, N.P.S., Colliver, D.W., Eichenberger, M.R. et al. Dig Dis Sci (2007) 52: 2716. doi:10.1007/s10620-006-9208-z

Abstract

Inflammatory bowel disease (IBD; MIM# 266600) is subdivided on the basis of clinical findings as either Crohn’s disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC). Three previously described mutations within the IBD susceptibility gene CARD15 (R702W, G908R, 1007fs) increase susceptibility to CD with a terminal ileal and/or ileocolonic location and fibrostenosing behavior. We undertook an association study using 477 unrelated IBD patients (248 CD, 172 UC, 57 IC) and 104 population controls to determine whether these previously described associations could be replicated in a small, accurately phenotyped cohort. Case-control and family-based approaches were employed to analyze CARD15 mutant allele and haplotype data. Analyses were initially performed in unstratified IBD cohorts. The R702W mutant allele was associated with CD on case-control analysis (q=0.036, P=.004), and 1007fs with CD on pedigree disequilibrium testing (P=.020). All 3 CARD15 mutations increased susceptibility to a variety of CD subphenotypic manifestations, including early-onset CD in individuals with a family history of IBD, and CD complicated by extraintestinal disease. We also present evidence to suggest that R702W may predispose to a more generalized form of CD. Additionally, we confirm that CARD15 mutations are associated with terminal ileal/ileocolonic, and to a lesser extent, fibrostenosing CD.

Keywords

Inflammatory bowel disease Crohn’s disease CARD15 Association studies Disease susceptibility 

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Nigel P. S. Crawford
    • 1
  • Daniel W. Colliver
    • 1
  • M. Robert Eichenberger
    • 1
  • Alisa A. Funke
    • 1
  • Valentina Kolodko
    • 1
  • Gary A. Cobbs
    • 2
  • Robert E. Petras
    • 3
  • Susan Galandiuk
    • 1
    • 4
  1. 1.Price Institute for Surgical Research, Department of SurgeryUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Department of BiologyUniversity of LouisvilleLouisvilleUSA
  3. 3.Ameripath Institute of Gastrointestinal Pathology and Digestive DiseaseOakwood VillageUSA
  4. 4.Department of SurgeryUniversity of LouisvilleLouisvilleUSA

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