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Future searches for genetic markers of how Crohn’s disease (CD) progresses will need to stratify patients by disease aggressiveness, site, and smoking, as each influences the early course of the disease. As importantly, NOD2/CARD15 genotype has no influence, according to the first study to use a validated classification of CD phenotype. Reliable predictors of disease course will mean patients receive optimal management early on.
The study looked for links between rapid progression of CD five years after diagnosis according to the Vienna classification and demographic, genetic, and disease variables.
Disease site and severity (number of flares/year) only were independent influences, according to multivariate analysis. Disease in the ileum significantly increased progression from initial non-stricturing, non-penetrating CD to stricturing CD five years later, and severity and smoking to progression to penetrating CD. For penetrating versus stricturing CD the markers were site and severity and familial disease. NOD2/CARD15 genotype bore no relation to disease state after five years. Overall, 68% of 163 patients with confirmed non-stricturing, non-penetrating CD initially had this disease pattern five years later, 11% had a stricturing form, and 22% a penetrating form.
Three mutations in the NOD2/CARD15 gene are linked to CD in Caucasians, but only in a quarter to a half of cases. CD is phenotypically very variable, and the stricturing and penetrating forms have more complications and need for operations. The investigators had already shown that the disease changed over time—from mostly non-structuring, non-penetrating to structuring or penetrating some 25 years later.
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