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Genetic risk factors for Clostridium difficile infection in ulcerative colitis

This month's issue of the Alimentary Pharmacology & Therapeutics evaluates genetic risk factors for Clostridium difficile infection in ulcerative colitis.

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Patients with inflammatory bowel disease are at higher risk for Clostridium difficile infection.

Disruption of gut microbiome and interaction with the intestinal immune system are essential mechanisms for pathogenesis of both Clostridium difficile infection and inflammatory bowel disease.

Dr Ananthakrishnan from Massachusetts, USA and fellow researchers conducted whether genetic polymorphisms associated with susceptibility to inflammatory bowel disease are also associated with risk of Clostridium difficile infection is unknown.

The team evaluated a well-characterized and genotyped cohort of patients with ulcerative colitis to identify clinical risk factors for Clostridium difficile.

The researchers examined if any of the inflammatory bowel disease genetic risk loci were associated withClostridium difficile infection, and compared the performance of predictive models using clinical and genetic risk factors in determining risk of Clostridium difficile infection.

The doctors used a prospective registry of patients from a tertiary referral hospital.

Medical record review was performed to identify all ulcerative colitis patients within the registry with a history of Clostridium difficile infection.

The genetic loci explained 28% of the variance in C difficile risk
Alimentary Pharmacology & Therapeutics

All patients were genotyped on the Immunochip.

The doctors examined the association between the 163 risk loci for inflammatory bowel disease, and risk of Clostridium difficile using a dominant genetic model.

Model performance was examined using receiver operating characteristics curves.

The study included 319 patients of whom 29 developed Clostridium difficile infection.

Female gender and pancolitis were associated with increased risk, while use of anti-TNF was protective against Clostridium difficile infection.

The researchers identified 6 genetic polymorphisms including those at TNFRSF14 that were associated with increased risk while 2 loci were inversely associated.

The research team found that none of the clinical parameters retained significance after adjusting for genetics.

Presence of at least 1 high-risk locus was associated with an increase in risk for Clostridium difficile infection.

Compared to 11% for a clinical model, the genetic loci explained 28% of the variance in Clostridium difficile risk.

Dr Ananthakrishnan's team concludes, "Host genetics may influence susceptibility to Clostridium difficile infection in patients with ulcerative colitis."

Aliment Pharmacol & Ther 2013: 38(5) 522530
06 September 2013

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