Reduced CFTR function and the pathobiology of idiopathic pancreatitis.
Idiopathic chronic pancreatitis (ICP) is the leading cause of chronic pancreatitis in children and nonalcoholic adults. The risk of developing ICP is increased in individuals who have mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). In studies from the United States and France, the risk of ICP is increased about 40-fold by having two abnormal copies of the CFTR gene, about 14-fold by having the N34S PSTI mutation, and about 500-fold by having both. When ICP patients have two abnormal copies of the CFTR gene, there is also evidence of reduced residual CFTR protein function in extrapancreatic tissues based on clinical findings and nasal ion transport responses. Thus, pancreatitis risk is highest in individuals who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI). These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the diagnosis and pathogenesis of pancreatitis.
Duke Scholars
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Related Subject Headings
- Trypsin Inhibitors
- Prevalence
- Pancreatitis
- Mutation
- Humans
- Genotype
- Gastroenterology & Hepatology
- Cystic Fibrosis Transmembrane Conductance Regulator
- Cystic Fibrosis
- Chronic Disease
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Trypsin Inhibitors
- Prevalence
- Pancreatitis
- Mutation
- Humans
- Genotype
- Gastroenterology & Hepatology
- Cystic Fibrosis Transmembrane Conductance Regulator
- Cystic Fibrosis
- Chronic Disease