Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen

Z. Nemoda, Niels Teich, Christin Hugenberg, Miklós Sahin-Tóth

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background/Aims: Mesotrypsin is a minor pancreatic digestive enzyme that degrades dietary trypsin inhibitors in the gut. In this study, we tested the hypothesis that the E32del genetic variant of mesotrypsin might represent a risk factor for the development of chronic pancreatitis, as a result of enhanced degradation of pancreatic secretory trypsin inhibitor. Methods: We screened 97 German patients with chronic pancreatitis of alcoholic etiology and 109 healthy controls for the presence of the E32del variant and characterized the biochemical properties of E32del mesotrypsinogen. Results: Higher allele frequency of the E32del variant was detected in the control population (25.7 vs. 18.0%), but the difference was not significant (p = 0.062). Recombinant E32del mesotrypsin exhibited normal catalytic activity, characteristic inhibitor resistance and inability to activate pancreatic zymogens. Degradation of trypsin inhibitors was unaffected by the E32del genotype. Interestingly, mesotrypsinogen-E32del was biochemically distinguishable from mesotrypsinogen by its faster activation with bovine enterokinase, while activation by human enterokinase, trypsin or cathepsin B was unchanged. Conclusion: The results classify E32del mesotrypsinogen as a frequent polymorphic variant, which is not associated with chronic alcoholic pancreatitis.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalPancreatology
Volume5
Issue number2-3
DOIs
Publication statusPublished - 2005

Fingerprint

Chronic Pancreatitis
Enteropeptidase
Molecular Biology
Trypsin Inhibitors
Kazal Pancreatic Trypsin Inhibitor
Alcoholic Pancreatitis
Cathepsin B
Enzyme Precursors
Gene Frequency
Trypsin
Genotype
Enzymes
Population

Keywords

  • Alcoholic pancreatitis
  • Chronic pancreatitis
  • Kazal-type 1
  • Serine protease inhibitor
  • Trypsinogen activation
  • Trypsinogen mutations

ASJC Scopus subject areas

  • Endocrinology
  • Gastroenterology

Cite this

Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen. / Nemoda, Z.; Teich, Niels; Hugenberg, Christin; Sahin-Tóth, Miklós.

In: Pancreatology, Vol. 5, No. 2-3, 2005, p. 273-278.

Research output: Contribution to journalArticle

Nemoda, Z. ; Teich, Niels ; Hugenberg, Christin ; Sahin-Tóth, Miklós. / Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen. In: Pancreatology. 2005 ; Vol. 5, No. 2-3. pp. 273-278.
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