Genomic medicine in inflammatory bowel disease

Voskuil, M., 2020, [Groningen]: University of Groningen. 242 p.

Research output: ThesisThesis fully internal (DIV)

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  • Title and contents

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  • Chapter 1

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  • Chapter 2

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  • Chapter 3

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  • Chapter 4

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  • Chapter 5

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  • Chapter 6

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  • Chapter 7

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  • Chapter 8

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  • Chapter 9

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  • Chapter 10

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  • Chapter 11

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  • Appendices

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  • Complete thesis

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  • Propositions

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Inflammatory bowel disease (IBD) is a term for two conditions (Crohn’s disease [CD] and ulcerative colitis [UC]) that are characterised by chronic inflammation of the gastrointestinal tract. Clinical symptoms of IBD include recurrent episodes of abdominal pain, diarrhoea, and weight loss. The exact cause of IBD remains unknown, but IBD is likely to be the result of a defective immune response to enteric bacteria in a genetically susceptibly individual. The first part of this thesis has focused on causal genes for the onset of IBD, and it has been demonstrated that specific intestinal T-cell subsets express these genes. In turn, it is hypothesised that these specific immune cell subsets are detrimental to disease mechanisms, and therefore potential targets for therapeutic intervention. The course IBD takes over time is unpredictable and heterogeneous, and there is a need for better patient stratification to aid clinical decision making. In the second part of this thesis it has been demonstrated that patients with a high genetic risk of disease susceptibility are also at risk of specific clinical aspects of disease such as disease location or disease behaviour. Adverse reactions and therapeutic failure are common in the management of IBD. In the final part of this thesis, several genetic mutations that predict adverse reactions to therapies used in the management of IBD have been identified. It has been demonstrated that if patients were to be genotyped prior to initiation of treatment, subsequent genotype-based therapies would lead to a decrease in adverse reactions.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Award date9-Nov-2020
Place of Publication[Groningen]
Publication statusPublished - 2020

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