Genetic aspects of chronic pancreatitis.
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S.l. : s.n.
Number of pages
RU Radboud Universiteit Nijmegen, 24 oktober 2005
Promotor : Jansen, J.B.M.J. Co-promotor : Drenth, J.P.H.
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SubjectUMCN 5.1: Genetic defects of metabolism
Chronic pancreatitis (CP) is a progressive inflammatory disorder. A key characteristic of the condition is severe recurrent abdominal pain. The origin of CP is mixed, with about 70% of the cases being attributed to alcohol abuse even though 95% of all alcoholics never develop CP. Approximately half a century ago, it was perceived that CP clusters in selected families, suggesting an inherited disease in these patients. By now there is universal recognition that multiple factors, including genetic factors, may ultimately lead to CP. Several genetic risk factors for CP have been identified recently. This thesis addresses a number of studies on genetic variations in detoxification enzymes and the risk for CP. We found that genetic predisposition for CP might be partly the result of polymorphisms in detoxification enzymes. In addition, the contribution of oxidative stress in CP is described. We found a lower antioxidant capacity and more oxidative damage in CP patients as compared to healthy controls, suggesting that oxidative stress might contribute to the pathogenesis of CP.In conclusion, molecular and genetic analyses for evaluation of pancreatic diseases will become important in future. Identification of key mutations in pancreatic-associated genes will provide important information on risk of developing CP. Moreover, mutation detection will assist in early diagnosis and helps to determine the aetiology of CP. Besides, knowledge on specific polymorphisms will help understanding of gene-environment interactions and knowledge of functional consequences of gene defects may help developing new therapeutic interventions. Finally, identification of functional gene mutations for CP is important for patients who are seeking answers to the question why they have developed CP and will be of help in family planning decisions. This thesis is a start for the research at some genetic aspects of CP and might direct future research on the molecular mechanisms of chronic pancreatitis.
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