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Title: Clinical and histological implications of genotyping in Crohn's disease
Author: Hanson, Catherine Elisabeth
Awarding Body: University of Newcastle Upon Tyne
Current Institution: University of Newcastle upon Tyne
Date of Award: 2011
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Crohn’s disease is a common inflammatory bowel disease affecting approximately 1 in 1000 of the population in the UK. Surgery for Crohn’s disease is common with the majority of patients requiring surgery at some point in the course of the disease. Both genetic and environmental factors influence Crohn’s disease. Smoking significantly influences the disease course in Crohn’s disease with more frequent relapses and increased need for surgery. Recent research had concentrated on the genes predisposing to the development of Crohn’s disease. In 2001 the CARD15 (NOD2) gene was identified and since then ~30 genes have been found to be associated with Crohn’s disease. This thesis aimed to investigate the influence of CARD15 (NOD2) on the time to second operation in terminal ileal Crohn’s disease. Crohn’s disease affects all parts of the gastrointestinal tract but particularly the terminal ileum. A particular cell type, the Paneth cell, has been implicated in the pathogenesis of Crohn’s disease. Paneth cells are located at the base of Crypts of Liberkühn throughout the small intestine but are found in greatest numbers in the terminal ileum. Paneth cells contain and secrete antimicrobial peptides in response to bacterial products. They have been found to express CARD15 (NOD2). The expression of antimicrobial peptides and the CARD15 (NOD2) genotype were investigated using the technique of in situ hibridization. There are well characterized histological features of Crohn’s disease. The are no known histological features of Crohn’s disease associated with the CARD15 (NOD2) genotype. These features were investigated. Osteoporosis is an important complication of Crohn’s disease and it’s treatment. Predictors of those at risk for the development of Crohn’s disease would be clinically useful in targeting therapy. Genetic influences on bone mineral density and Crohn’s disease were investigated. Recent publications have furthered our knowledge of the genetic factors influencing the development of Crohn’s disease. The Newcastle cohort of patients contributed to this knowledge. The aim of this study was to investigate survival to second operation in terminal ileal Crohn’s disease. The effect of environmental factors including smoking and exposure to thiopurines was investigated. In particular the effect of CARD15(NOD2) genotype and carriage of the 5q31 haplotype was studied.
Supervisor: Not available Sponsor: Margaret Simm Legacy ; National Association for Colitis and Crohn's Disease
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available