An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or CTRC Genetic Variants in Patients With Idiopathic Pancreatitis

Am J Gastroenterol. 2017 Aug;112(8):1320-1329. doi: 10.1038/ajg.2017.106. Epub 2017 Apr 25.


Objectives: We evaluated factors associated with pathogenic genetic variants in patients with idiopathic pancreatitis.

Methods: Genetic testing (PRSS1, CFTR, SPINK1, and CTRC) was performed in all eligible patients with idiopathic pancreatitis between 2010 to 2015. Patients were classified into the following groups based on a review of medical records: (1) acute recurrent idiopathic pancreatitis (ARIP) with or without underlying chronic pancreatitis; (2) idiopathic chronic pancreatitis (ICP) without a history of ARP; (3) an unexplained first episode of acute pancreatitis (AP)<35 years of age; and (4) family history of pancreatitis. Logistic regression analysis was used to determine the factors associated with pathogenic genetic variants.

Results: Among 197 ARIP and/or ICP patients evaluated from 2010 to 2015, 134 underwent genetic testing. A total of 88 pathogenic genetic variants were found in 64 (47.8%) patients. Pathogenic genetic variants were identified in 58, 63, and 27% of patients with ARIP, an unexplained first episode of AP <35 years of age, and ICP without ARP, respectively. ARIP (OR: 18.12; 95% CI: 2.16-151.87; P=0.008) and an unexplained first episode of AP<35 years of age (OR: 2.46; 95% CI: 1.18-5.15; P=0.017), but not ICP, were independently associated with pathogenic genetic variants in the adjusted analysis.

Conclusions: Pathogenic genetic variants are most likely to be identified in patients with ARIP and an unexplained first episode of AP<35 years of age. Genetic testing in these patient populations may delineate an etiology and prevent unnecessary diagnostic testing and procedures.

MeSH terms

  • Adult
  • Aged
  • Carrier Proteins / genetics*
  • Chymotrypsin / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pancreatitis / genetics*
  • Retrospective Studies
  • Trypsin / genetics*
  • Trypsin Inhibitor, Kazal Pancreatic


  • Carrier Proteins
  • SPINK1 protein, human
  • Trypsin Inhibitor, Kazal Pancreatic
  • Chymotrypsin
  • chymotrypsin C
  • PRSS1 protein, human
  • Trypsin