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Genetic factors with an increased susceptibility to develop Crohn's disease

The most recent issue of Gut investigates genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype.

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Through genome-wide association scans and meta-analyses thereof, over 70 genetic loci are significantly associated with CD.

Dr Isabelle Cleynen and colleagues from Belgium investigated the influence of Crohn's disease single nucleotide polymorphisms and basic patient characteristics on CD clinical course, and develop statistical models to predict CD clinical course.

This retrospective study included 1528 patients with CD with more than 10 years of follow-up from 8 European referral hospitals.

CD outcomes of interest were ileal, colonic, and ileocolonic disease location, stenosing or penetrating behavior, perianal disease, extraintestinal manifestations, and bowel resection.

The team defined a complicated disease course as stenosing or penetrating behavior, perianal disease and/or bowel resection.

Immunomodulator use within 3 years after diagnosis led to a reduction in bowel stenoses
Gut

Association between Crohn's disease single nucleotide polymorphisms or patient characteristics, and specified outcomes was studied.

Several Crohn's disease single nucleotide polymorphisms, and clinical characteristics were statistically associated with outcomes of interest.

The research team found that the NOD2 gene was the most important genetic factor, being an independent predictive factor for ileal location, stenosing and penetrating CD behaviors, and need for surgery, and as such was also the strongest factor associated with a complicated disease course.

The team observed that immunomodulator use within 3 years after diagnosis led to a reduction in bowel stenoses, and surgical rate.

Association between each outcome and genetic scores, created using significant SNPs in the univariate analysis, revealed large differences in the probability of developing fistulising disease, need for surgery, and stenosing disease among patients with low and high score.

Dr Cleynen's team concludes, "This large multicenter cohort study has found several genetic and clinical factors influencing the clinical course of CD."

"NOD2 and early immunomodulator use are the clinically most meaningful predictors for its clinical course."

Gut 2013; 62: 1556-1565
11 October 2013

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