Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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The Role of Genetics in Inflammatory Bowel Disease

Author(s): Liesbet Henckaerts, Carolina Figueroa, Severine Vermeire, Miquel Sans.

Abstract:

The volume of research undertaken on the genetic susceptibility of inflammatory bowel disease (IBD) has been tremendous. Genome-wide linkage studies pointed towards more than 10 chromosomal regions and fine-mapping of these regions led to the identification of a number of genes, including CARD15 (NOD2), DLG5, OCTN1 and 2, TLR4 and CARD4 (NOD1). With the recent completion of the human genome project, whole genome association studies (WGAS) have now become possible and have identified additional genes (IL23R, IRGM, PTGER4, ATG16L1) for Crohns disease and ulcerative colitis, that have subsequently been replicated. At present, the CARD15 gene is still the most understood susceptibility gene, explaining around 20% of the genetic predisposition to Crohns disease. Prediction of disease phenotype and response to the main therapies has for many years been a dream for physicians treating IBD patients. Only now, we start to accumulate some evidence proving that genetic factors indeed influence both the clinical course of IBD patients and their likelihood of responding to certain therapies. In the coming years, we expect an exponential increase in the efforts devoted to research in this area. The optimal prediction of both disease behaviour and response to therapy might result from complex combinations of clinical, biochemical, serological and genetic factors.

Keywords: CARD15 Gene, NOD2 protein, pattern recognition receptors, MDR1 polymorphisms, interleukin 23 receptor, immunosuppressive therapy

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Article Details

VOLUME: 9
ISSUE: 5
Year: 2008
Page: [361 - 368]
Pages: 8
DOI: 10.2174/138945008784221161
Price: $58