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

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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.

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Authors and Affiliations

  1. Price Institute for Surgical Research, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA

    Nigel P. S. Crawford, Daniel W. Colliver, M. Robert Eichenberger, Alisa A. Funke, Valentina Kolodko & Susan Galandiuk

  2. Department of Biology, University of Louisville, Louisville, Kentucky, USA

    Gary A. Cobbs

  3. Ameripath Institute of Gastrointestinal Pathology and Digestive Disease, Oakwood Village, Ohio, USA

    Robert E. Petras

  4. Department of Surgery, University of Louisville, Louisville, KY, 40292, USA

    Susan Galandiuk

Authors
  1. Nigel P. S. Crawford
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  2. Daniel W. Colliver
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  3. M. Robert Eichenberger
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  4. Alisa A. Funke
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  5. Valentina Kolodko
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  6. Gary A. Cobbs
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  7. Robert E. Petras
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  8. Susan Galandiuk
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Correspondence to Susan Galandiuk.

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Crawford, N.P.S., Colliver, D.W., Eichenberger, M.R. et al. CARD15 Genotype-Phenotype Relationships in a Small Inflammatory Bowel Disease Population with Severe Disease Affection Status. Dig Dis Sci 52, 2716–2724 (2007). https://doi.org/10.1007/s10620-006-9208-z

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  • DOI: https://doi.org/10.1007/s10620-006-9208-z

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