Genetic risk variants in intestinal inflammatory disorders
Abstract
This thesis includes work on the genetics of intestinal inflammatory disorders, concentrating
on coeliac disease and Crohn’s disease. It explores how common genetic variants influence
risk of complex phenotypes including immunological intolerance to gluten (coeliac disease)
and intolerance to therapeutic agents (azathioprine and mercaptopurine) used in the
treatment of intestinal inflammatory diseases. Finally it presents work aiming to move from
genetic associations with complex phenotypes to understanding of how these variants
modulate immunological processes.
Results of a large genome wide association study that identified more than 13 new genetic risk
regions influencing susceptibility to coeliac disease are presented. Results of a genome wide
association study of azathioprine and 6-mercaptopurine-induced pancreatitis in inflammatory
bowel disease-affected individuals are presented. Finally, a cell cytokine release assay for the
prostaglandin EP4 receptor was developed, with a view to investigating how SNPs associated
with Crohn’s disease in the 5p13.1 region influence EP4 receptor signalling and contribute to
disease pathogenesis. This work highlights some of the challenges in moving from SNP-disease
associations identified in GWASs to understanding how genetic variants change biological
processes.
Authors
Dubois, Patrick Charles AlexanderCollections
- Theses [3702]