A functional genetics approach to increase our understanding of fibrostenosis in patients with Crohn's disease.

01 January 2020 → 31 December 2023
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Gastro-enterology
Fibrosis candidate genes
Project description

Crohn’ disease (CD) is a chronic inflammatory disease of the intestine that represents an important personal an societal health problem While the progression of the disease is heterogeneous, more than 50% of patients will require surgery The most important indication for surgery is fibrostenosis, caused by the excess deposition of components generated during wound healing, which in time progressively leads to narrowing of the intestinal lumen and the formation of irreversible strictures Today, we cannot predict who will develop these strictures, and little is known about the molecular pathways involved

Here, we focus on the genetic contribution to the development of strictures in CD patients We recently conducted a well-controlled and replicated genetic study, using strict definitions of this complication based on CT scans and pathology reports As such, we identified associated genetic loci and built a genetic risk score for fibrostenotic CD Next we aim to identify mutations in candidate genes within these associated loci, perform functional analysis of two risk genes in primary effector cells of fibrosis and prospectively test the genetic risk score in newly diagnosed patients to determine its potential as prognostic tool for fibrostenotic CD Together, these data will contribute to understanding the pathophysiology of fibrosis in CD pathogenesis and aid in patient stratification necessary to initiate clinical trials