Chronic pancreatitis: genetics and pathogenesis

Annu Rev Genomics Hum Genet. 2009;10:63-87. doi: 10.1146/annurev-genom-082908-150009.


Chronic pancreatitis (CP) is a persistent inflammation of the pancreas. Over the past 12 years, genetic studies of hereditary, familial, and idiopathic forms of CP have made great progress in defining the disease pathogenesis. Identification of gain-of-function missense and copy number mutations in the cationic trypsinogen gene (PRSS1) and loss-of-function variants in both the pancreatic secretory trypsin inhibitor (SPINK1) and chymotrypsinogen C (CTRC) genes has firmly established the pivotal role of prematurely activated trypsin within the pancreas in the etiology of CP. Loss-of-function variants in the cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-sensing receptor (CASR) genes also increase the risk of CP. Here, we review recent developments in this rapidly evolving field, highlight the importance of gene-gene and gene-environment interactions in causing the disease, and discuss the opportunities and challenges in identifying novel genetic factors that affect susceptibility/resistance to CP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Activation
  • Genetic Predisposition to Disease
  • Humans
  • Life Style
  • Pancreatitis, Chronic / enzymology
  • Pancreatitis, Chronic / etiology
  • Pancreatitis, Chronic / genetics*
  • Risk Factors