Skip to main content

Advertisement

SpringerLink
Log in

Genetic testing in acute and chronic pancreatitis

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Hereditary pancreatitis (HP) is clinically indistinguishable from pancreatitis with other causes. Patients with HP have an increased chance of developing pancreatitis. Mutations in the cationic trypsinogen gene appear to cause most HP, although there is evidence for mild genetic heterogeneity with defects in other genes. Trypsin stabilization and protection from autolysis appear to play a central role in the pathogenesis of pancreatitis. The role of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) as well as the pancreatic secretory trypsin inhibitor (PSTI) in patients with pancreatitis is intriguing but as yet incompletely understood. Genetic testing may help to identify and manage patients with HP. Healthcare professionals should understand the elements necessary for obtaining informed consent for patients undergoing these tests, the limits in interpreting test results, and the psychosocial issues that may arise from genetic testing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Comfort M, Steinberg A: Pedigree of a family with hereditary chronic relapsing pancreatitis. Gastroenterology 1952, 21:54–63.

    PubMed  CAS  Google Scholar 

  2. Perrault J: Hereditary pancreatitis, historical perspectives. Med Clin North Am 2000, 84:519–529.

    Article  PubMed  CAS  Google Scholar 

  3. Whitcomb DC: Hereditary pancreatitis: new insights into acute and chronic pancreatitis. Gut 1999, 45:317–322. The author describes the discovery of the trypsinogen gene and how it causes the phenotype of HP, and puts forward the SAPE hypothesis for the progression of acute to chronic pancreatitis.

    Article  PubMed  CAS  Google Scholar 

  4. Sossenheimer MJ, Aston CE, Preston RA, et al., for the Midwest Multicenter Pancreatic Study Group: Clinical characteristics of hereditary pancreatitis in a large family, based on high-risk haplotype. Am J Gastroenterol 1997, 92:1113–1116.

    PubMed  CAS  Google Scholar 

  5. Applebaum SE, Kant JA, Whitcomb DC, Ellis IH: Genetic testing, counseling, laboratory and regulatory issues and the EUROPAC protocol for ethical research in multicenter studies of inherited pancreatic diseases. Med Clin North Am 2000, 84:575–588. This article explains the indications, implications, limitations, and risks of genetic testing in general and of HP in particular.

    Article  PubMed  CAS  Google Scholar 

  6. Lowenfels AB, Maisonneuve P, DiMagno EP, et al.: Hereditary pancreatitis and the risk of pancreatic cancer: International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 1997, 89:442–446.

    Article  PubMed  CAS  Google Scholar 

  7. Hengstler JG, Bauer A, Wolf HK, et al.: Mutation analysis of the cationic trypsinogen gene in patients with pancreatic cancer. Anticancer Res 2000, 20:2967–2974.

    PubMed  CAS  Google Scholar 

  8. Le Bodic L, Schnee M, Georgelin T, et al.: An exceptional genealogy for hereditary chronic pancreatitis. Dig Dis Sci 1996, 41:1504–1510.

    Article  PubMed  CAS  Google Scholar 

  9. Whitcomb DC, Preston RA, Aston CE, et al.: A gene for hereditary pancreatitis maps to chromosome 7q35. Gastroenterology 1996, 110:1975–1980.

    Article  PubMed  CAS  Google Scholar 

  10. Le Bodic L, Bignon JD, Raguenes O, et al.: The hereditary pancreatitis gene maps to long arm of chromosome 7. Hum Mol Genet 1996, 5:549–554.

    Article  PubMed  Google Scholar 

  11. Pandya A, Blanton SH, Landa B, et al.: Linkage studies in a large kindred with hereditary pancreatitis confirms mapping of the gene to a 16-cM region on 7q. Genomics 1996, 38:227–230.

    Article  PubMed  CAS  Google Scholar 

  12. Whitcomb DC, Gorry MC, Preston RA, et al.: Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996, 14:141–145.

    Article  PubMed  CAS  Google Scholar 

  13. Ulrich CD II, Kopras E, Wu Y, Ward S: Hereditary pancreatitis: epidemiology, molecules, mutations, and models. J Lab Clin Med 2000, 136:260–274. The authors review the pathophysiology of HP, the relevance of HP studies to nonhereditary pancreatitis, and reasons for the lack of translational impact of current models of pancreatitis. They also discuss what may be achieved with transgenic models.

    Article  PubMed  CAS  Google Scholar 

  14. Chen J-M, Ferec C: Genes, cloned cDNAs, and proteins of human trypsinogens and pancreatitis-associated cationic trypsinogen mutations. Pancreas 2000, 21:57–62.

    Article  PubMed  Google Scholar 

  15. Figarella C, Clemente F, Guy O: On zymogens of human pancreatic juice. FEBS Lett 1969, 3:351–353.

    Article  PubMed  CAS  Google Scholar 

  16. Scheele G, Bartelt D, Bieger W: Characterization of human exocrine pancreatic proteins by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis. Gastroenterology 1981, 80:461–473.

    PubMed  CAS  Google Scholar 

  17. Sahin-Toth M, Graf L, Toth M: Trypsinogen stabilization by mutation Arg117>His: a unifying pathomechanism for hereditary pancreatitis? Biochem Biophys Res Commun 1999, 264:505–508. This article and the next are accounts of experimental studies in rats that support the proposed central role of trypsinogen stabilization in the pathogenesis of HP and the dual regulation of trypsinogen by calcium.

    Article  PubMed  CAS  Google Scholar 

  18. Sahin-Toth M and Toth M: High-affinity Ca2+ binding inhibits autoactivation of rat trypsinogen. Biochem Biophpys Res Commun 2000, 275:668–671. See annotation for reference [17].

    Article  CAS  Google Scholar 

  19. Sahin-Toth M, Toth M: Gain-of-function mutations associated with hereditary pancreatitis enhance autoactivation of human cationic trypsinogen. Biochem Biohpys Res Commun 2000, 278:286–289.

    Article  CAS  Google Scholar 

  20. Antonarakis SE: Recommendations for a nomenclature system for human gene mutations. Hum Mutat 1998, 11:1–3.

    Article  PubMed  CAS  Google Scholar 

  21. Keim V, Teich N, Mossner J: Trypsinogen mutations in hereditary pancreatitis: which nomenclature is convenient? Gut 2000, 46:873.

    Article  PubMed  CAS  Google Scholar 

  22. Gorry MC, Gabbaizedeh D, Furey W, et al.: Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis. Gastroenterology 1997, 113:1063–1068.

    Article  PubMed  CAS  Google Scholar 

  23. Sahin-Toth M: Human cationic trypsinogen: role of Asn-21 in zymogen activation and implications in hereditary pancreatitis. J Biol Chem 2000, 275:22750–22755.

    Article  PubMed  CAS  Google Scholar 

  24. Chen J-M, Ferec C: Origin and implication of the hereditary pancreatitis-associated N21I mutation in the cationic trypsinogen gene. Hum Genet 2000, 106:125–126.

    Article  PubMed  CAS  Google Scholar 

  25. O'Reilly DA, Kingsnorth AN: Hereditary pancreatitis and mutations of the cationic trypsinogen gene. Br J Surg 2000, 87:708–717.

    Article  PubMed  Google Scholar 

  26. Creighton JE, Lyall R, Wilson DI, et al.: Mutations of the cationic trypsinogen gene in patients with hereditary pancreatitis. Br J Surg 2000, 87:170–175.

    Article  PubMed  CAS  Google Scholar 

  27. Nishimori I, Kamakura M, Fujikawa-Adachi K, et al.: Mutations in exons 2 and 3 of the cationic trypsinogen gene in Japanese families with hereditary pancreatitis. Gut 1999, 44:259–263.

    Article  PubMed  CAS  Google Scholar 

  28. Witt H, Luck W, Becker M: A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis. Gastroenterology 1999, 117:7–10.

    Article  PubMed  CAS  Google Scholar 

  29. Chen J-M, Ferec C: Molecular basis of hereditary pancreatitis. Eur J Hum Gen 2000, 8:473–479. The authors review the molecular basis of HP, the genetic heterogeneity of HP, and the role of CF mutations in patients with pancreatitis.

    Article  CAS  Google Scholar 

  30. Ferec C, Raguenes O, Salomon R, et al.: Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis. J Med Genet 1999, 36:228–232.

    PubMed  CAS  Google Scholar 

  31. Teich N, Ockenga J, Hoffmeister A, et al.: Chronic pancreatitis associated with an activation peptide mutation that facilitates trypsin activation. Gastroenterology 2000, 119:461–465.

    Article  PubMed  CAS  Google Scholar 

  32. Bartness MA, Duerr RH, Ford MA, et al.: A new hereditary pancreatitis gene may map to chromosome 12. Pancreas 1998, 17:426.

    Google Scholar 

  33. Ravnik-Glavac M, Glavac D, di Sant Agnese P, et al.: Cystic fibrosis gene mutations detected in hereditary pancreatitis. Pflugers Arch 1996, 431:R191-R192.

    Article  PubMed  CAS  Google Scholar 

  34. Sharer N, Schwarz M, Malone G, et al.: Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med 1998, 339:645–652.

    Article  PubMed  CAS  Google Scholar 

  35. Cohn JA, Friedman KJ, Noone PG, et al.: Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998, 339:653–658.

    Article  PubMed  CAS  Google Scholar 

  36. Durie PR: Pancreatitis and mutations of the cystic fibrosis gene. N Engl J Med 1998, 339:687–688.

    Article  PubMed  CAS  Google Scholar 

  37. Pfutzer RH, Barmada MM, Brunskill APJ, et al.: SPINK/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis. Gastroenterology 2000, 119:615–623.

    Article  PubMed  CAS  Google Scholar 

  38. Witt H, Luck W, Hennies HC, et al.: Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet 2000, 25:213–216.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Molecular Diagnostics, University of Pittsburgh Medical Center, S701 Scaife Hall, 3550 Terrace Street, 15213, Pittsburgh, PA, USA

    Raj K. Rolston MD & Jeffrey A. Kant MD, PhD

Authors
  1. Raj K. Rolston MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey A. Kant MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rolston, R.K., Kant, J.A. Genetic testing in acute and chronic pancreatitis. Curr Gastroenterol Rep 3, 115–120 (2001). https://doi.org/10.1007/s11894-001-0007-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-001-0007-6

Keywords

Search

Navigation