The genetics of inflammatory bowel disease: Diagnostic and therapeutic implications

Carmen Cuffari

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Background: The genetics of inflammatory bowel diseases (IBD) has brought new insight into the spectrum of disease phenotypes that are collectively labeled as either Crohn's disease or ulcerative colitis. In concert with the pharmacogenomics of drug therapy, it has led clinicians to develop the notion of a more tailored approach to therapy. Data sources: Articles were searched from PubMed (1995-2010) with key words "inflammatory bowel diseases", "Genetics", "pharmacogenomics". Results: Among all the putative susceptibility loci, the NOD2 gene has been the most studied and linked to an aggressive form of stricturing and perforating disease of the ileum. Other potential gene polymorphisms, including those encoding for the interleukin-23 receptor, have lent themselves to the recent development of potential novel immunosuppressive therapies. While the linkage of a number of autophagy genes with either Crohn's disease or ulcerative colitis has provided insight into the innate adaptive immune pathway's response to commensual intestinal bacteria. Pharmacogenetic polymorphisms of azathioprine metabolism have been shown to predict toxicity to anti-metabolite therapy. Patients with absent thiopurine methyl transferase enzyme activity are at risk for irreversible bone marrow suppression, and are not considered good candidates for either 6-mercaptopurine (6-MP) or azathioprine therapy. Conclusions: Ultimately, the correlation between these genotypes and clinical phenotype of disease will inevitably lead to an improved understanding of disease natural history and a more tailored approach to therapy. Although there is ongoing debate as to whether these inherent differences in enzyme activity can predict responsiveness to anti-metabolite therapy, some gastroenterologists do find value in 6-MP metabolite testing as a means of monitoring patient compliance and tailoring the dose of anti-metabolite therapy based on a perceived therapeutic window. In the future, patients with IBD will ultimately be categorized based on their genomic imprint to allow for a better delineation of disease phenotype. Furthermore, the application pharmacogenomics of drug therapy into clinical practice will be pivotal in maximizing treatment response while avoiding untoward side-effects.

Original languageEnglish (US)
Pages (from-to)203-209
Number of pages7
JournalWorld Journal of Pediatrics
Issue number3
StatePublished - Aug 2010


  • 6-mercaptopurine metabolites
  • genetics
  • inflammatory bowel diseases
  • pharmacogenomics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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