Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations.

Area of Science:

• Genetics and Molecular Biology
• Gastroenterology
• Pulmonology

Background:

• Nonalcoholic chronic pancreatitis is often idiopathic and linked to cystic fibrosis gene (CFTR) mutations.
• The correlation between pancreatitis risk and the number of CFTR mutations, ion transport function, or other gene mutations remains unclear.

Purpose of the Study:

• To investigate the association between CFTR and PSTI gene mutations and the risk of nonalcoholic chronic pancreatitis.
• To evaluate the role of extrapancreatic CFTR function in pancreatitis development.

Main Methods:

• Genotyping for common and rare CFTR mutations, PSTI (N34S), and PRSS1 mutations in 39 patients with idiopathic chronic pancreatitis.
• Assessing extrapancreatic CFTR function through clinical and physiological evaluations in select subjects.
• Analyzing the correlation between specific genotypes and pancreatitis risk.

Main Results:

• Mutations were found in 24 of 39 patients.
• Having two CFTR mutations increased pancreatitis risk ~40-fold; the N34S PSTI mutation increased risk ~20-fold; having both mutations increased risk ~900-fold.
• Subjects with two CFTR mutations exhibited abnormal ion transport, while those with only PSTI mutations had normal CFTR function.

Conclusions:

• Pancreatitis risk is associated with two CFTR mutations and impaired extrapancreatic CFTR function.
• The N34S PSTI mutation independently elevates pancreatitis risk.
• Genotype testing for CFTR and PSTI may aid in diagnosing nonalcoholic pancreatitis.