Prediction of Crohn's disease aggression through NOD2/CARD15 gene sequencing in an Australian cohort

AIM:To investigate the association between mutations in oligomerisation domain 2/caspase recruitment domains 15(NOD2/CARD15)and the natural history of Crohn’s disease(CD)to identify patients who would benefit from early aggressive medical intervention.METHODS:We recruited thirty consecutive unrelated CD patients with a history of ileo-caecal or small bowel resection during the period 1980-2000;Fifteen patients of these had post-operative relapse that required further surgery and fifteen did not.Full sequencing of the NOD2/CARD15 gene using dHPLC for exons 3,5,7,10 and 12 and direct sequencing for exons 2,4,6,8,9 and 11 was conducted.CD patients categorized as carrying variants were anyone with at least 1 variant of the NOD2/CARD15 gene.RESULTS:About 13.3%of the cohort(four patients)carried at least one mutant allele of 3020ins C of the NOD2/CARD15 gene.There were 20 males and 10females with a mean age of 43.3 years(range 25-69years).The mean follow up was 199.6 mo and a median of 189.5 mo.Sixteen sequence variations within the NOD2/CARD15 gene were identified,with 9 of them occurring with an allele frequency of greater than 10%.In this study,there was a trend to suggest that patients with the 3020ins C mutation have a higher frequency of operations compared to those without the mutation.Patients with the 3020insC mutation had a significantly shorter time between the diagnosis of CD and initial surgery.This study included Australian patients of ethnically heterogenous background unlike previous studies conducted in different countries.CONCLUSION:These findings suggest that patients carrying NOD2/CARD15 mutations follow a rapid and more aggressive form of Crohn’s disease showing a trend for multiple surgical interventions and significantly shorter time to early surgery.