Determination of the Relative Contribution of Three Genes-The Cystic Fibrosis Transmembrane Conductance Regulator Gene, the Cationic Trypsinogen Gene, and the Pancreatic Secretory Trypsin Inhibitor Gene-To the Etiology of Idiopathic Chronic Pancreatitis

Eur J Hum Genet. 2002 Feb;10(2):100-6. doi: 10.1038/sj.ejhg.5200786.


In the last 5 years, mutations in three genes, the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the pancreatic secretory trypsin inhibitor (PSTI) gene, have been found to be associated with chronic pancreatitis (CP). In this study, using established mutation screening methods, we systematically analysed the entire coding sequences and all exon/intron junctions of the three genes in 39 patients with idiopathic CP (ICP), with a view to evaluating the relative contribution of each gene to the aetiology of the disease. Our results demonstrate that, firstly, 'gain-of-function' mutations in the PRSS1 gene may occasionally be found in an obvious ICP subject. Secondly, presumably 'loss-of-function' mutations in the PSTI gene appear to be frequent, with a detection rate of at least 10% in ICP and, finally, abnormal CFTR alleles are common: at least 20% of patients carried one of the most common CFTR mutations, and about 10% of patients were compound heterozygotes, having at least one 'mild' allele. Thus, in total, about 30% of ICP patients carried at least one abnormal allele in one of the three genes, and this is the most conservative estimate. Moreover, a trans-heterozygous state with sequence variations in the PSTI/CFTR genes was found in three patients. However, an association between the 5T allele in intron 8 of the CFTR gene and ICP remains unproven.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Female
  • France
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mutation
  • Pancreatitis / etiology
  • Pancreatitis / genetics*
  • Trypsin Inhibitor, Kazal Pancreatic / genetics*
  • Trypsin Inhibitor, Kazal Pancreatic / metabolism
  • Trypsin*
  • Trypsinogen / genetics*
  • Trypsinogen / metabolism


  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsin Inhibitor, Kazal Pancreatic
  • Trypsinogen
  • PRSS1 protein, human
  • Trypsin