Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Objective: Thiopurines, (azathioprine and mercaptopurine), are approved drugs for maintaining remission in Crohn’s disease (CD). A recent genetic analysis showed a significant association between a risk allele in the ATG16L1 gene and response to thiopurines in patients with CD. Additionally, this risk allele caused a hyperactivity of the Rac1 protein via a diminished amount of the ATG16L1, leading to less autophagy and less migration. Thiopurines would be able to inhibit this hyperactivity of Rac1. Design: A retrospective study at the University Hospitals of Leuven was performed on 300 caucasian patients with CD, who initiated thiopurine monotherapy. The aim of the study was to evaluate associations between the ATG16L1 genotype, clinical characteristics and response to thiopurines. Response was defined as the use of thiopurine monotherapy for more than 1 year with less than 2 treatments of corticosteroids and no need for additional treatment. Results: 125 patients had response to thiopurines monotherapy, after a minimal follow up of 1 year. No statistically significant differences were observed between response and sex, smoking behaviour, disease behaviour, perianal disease or disease location. Responders to thiopurines less often carried the ATG16L1 minor allele compared to non-responders, though this was not statistically significant (54.8% vs 61.9%, p = 0.17, OR 0.76 [0.51-1.13]). Conclusions: We could not confirm an association between a ATG16L1 genetic variant and response to thiopurines. Inter-individual differences in response to thiopurines are still not fully understood and warrant further big cohort studies to identify predictive markers.