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Idiopathic Pancreatitis Related to CFTR: Complex Inheritance and Identification of a Modifier Gene
  1. Jonathan A. Cohn,
  2. Peadar G. Noone,
  3. Paul S. Jowell
  1. 1From the Duke University and Veterans Administration Medical Centers, Durham, NC (J.A.C., P.S.J.)
  2. 2University of North Carolina, Chapel Hill, NC (P.G.N.).
  1. Address correspondence to: Jonathan A. Cohn, MD, Duke University Medical CenterBox 3378, Durham, NC 27710. Email: cohn0001{at}


Idiopathic chronic pancreatitis (ICP) is the leading cause of nonalcoholic chronic pancreatitis. This study examined a series of patients with ICP to determine the prevalence and role of mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). Genetic testing was done in 39 patients with ICP. In this series, 17 patients had CFTR mutations and 9 had PSTI mutations. Pancreatitis risk was increased 14-fold by having the N34S PSTI mutation, 40-fold by having two abnormal copies of CFTR, and 600-fold by having both. In patients with two CFTR mutations, extrapancreatic clinical findings and nasal bioelectric responses suggested reduced residual CFTR protein function. Thus, pancreatitis risk showed complex inheritance and was 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 classification, diagnosis, and pathogenesis of pancreatitis.

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