Genetic Risk in Chronic Pancreatitis: The Trypsin-Dependent Pathway

Dig Dis Sci. 2017 Jul;62(7):1692-1701. doi: 10.1007/s10620-017-4601-3. Epub 2017 May 23.


Genetic investigations have provided unique insight into the mechanism of chronic pancreatitis in humans and firmly established that uncontrolled trypsin activity is a central pathogenic factor. Mutations in the PRSS1, SPINK1, and CTRC genes promote increased activation of trypsinogen to trypsin by stimulation of autoactivation or by impairing protective trypsinogen degradation and/or trypsin inhibition. Here we review key genetic and biochemical features of the trypsin-dependent pathological pathway in chronic pancreatitis.

Keywords: Chymotrypsin; Digestive enzymes; Pancreas; Pancreatitis; Trypsin inhibitor; Trypsinogen activation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Gene Expression Regulation / physiology*
  • Genetic Predisposition to Disease*
  • Humans
  • Mutation
  • Pancreatitis, Chronic / genetics*
  • Trypsin / metabolism*


  • Trypsin