Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis

Jonas Rosendahl, Niels Teich, Peter Kovacs, R. Szmola, Matthias Blüher, Thomas M. Gress, Albrecht Hoffmeister, Volker Keim, Matthias Löhr, Joachim Mössner, Renate Nickel, Johann Ockenga, Roland Pfützer, Hans Ulrich Schulz, Michael Stumvoll, Henning Wittenburg, Miklós Sahin-Tóth, Heiko Witt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background/Aims: A sustained imbalance of pancreatic proteases and their inhibitors seems to be important for the development of chronic pancreatitis (CP). Mesotrypsin (PRSS3) can degrade intrapancreatic trypsin inhibitors that protect against CP. Genetic variants that cause higher mesotrypsin activity might increase the risk for CP. Methods: We analyzed all 5 exons and the adjacent non-coding sequences of PRSS3 by direct sequencing of 313 CP patients and 327 controls. Additionally, exon 4 was investigated in 855 patients and 1,294 controls and a c.454+191G>A variant in 855 patients and 1,467 controls. The c.499A>G (p.T167A) variant was analyzed functionally using transiently transfected HEK 293T cells. Results: In the exonic regions, the previously described common c.94-96delGAG (p.E32del) variant and a novel p.T167A non-synonymous alteration were identified. Extended analysis of the p.T167A variant revealed no association to CP and in functional assays p.T167A showed normal secretion and activity. Variants of the intronic regions, including the extensively analyzed c.454+191G>A alteration, were not associated with the disease. Haplotype reconstruction using variants with a minor allele frequency of >1% revealed no CP-associated haplotype. Conclusions: Although the trypsin inhibitor-degrading activity qualified PRSS3 as a candidate for a novel CP susceptibility gene, we found no association between a specific variant or haplotype and CP in our cohort with a high suspicion of genetically determined disease.

Original languageEnglish
Pages (from-to)243-249
Number of pages7
JournalPancreatology
Volume10
Issue number2-3
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Chronic Pancreatitis
Genes
Haplotypes
Trypsin Inhibitors
Exons
HEK293 Cells
Protease Inhibitors
Gene Frequency

Keywords

  • Chronic pancreatitis
  • Haplotype
  • Mesotrypsinogen
  • PHASE v2.1
  • PRSS3
  • Variant

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Medicine(all)

Cite this

Rosendahl, J., Teich, N., Kovacs, P., Szmola, R., Blüher, M., Gress, T. M., ... Witt, H. (2010). Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis. Pancreatology, 10(2-3), 243-249. https://doi.org/10.1159/000243769

Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis. / Rosendahl, Jonas; Teich, Niels; Kovacs, Peter; Szmola, R.; Blüher, Matthias; Gress, Thomas M.; Hoffmeister, Albrecht; Keim, Volker; Löhr, Matthias; Mössner, Joachim; Nickel, Renate; Ockenga, Johann; Pfützer, Roland; Schulz, Hans Ulrich; Stumvoll, Michael; Wittenburg, Henning; Sahin-Tóth, Miklós; Witt, Heiko.

In: Pancreatology, Vol. 10, No. 2-3, 06.2010, p. 243-249.

Research output: Contribution to journalArticle

Rosendahl, J, Teich, N, Kovacs, P, Szmola, R, Blüher, M, Gress, TM, Hoffmeister, A, Keim, V, Löhr, M, Mössner, J, Nickel, R, Ockenga, J, Pfützer, R, Schulz, HU, Stumvoll, M, Wittenburg, H, Sahin-Tóth, M & Witt, H 2010, 'Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis', Pancreatology, vol. 10, no. 2-3, pp. 243-249. https://doi.org/10.1159/000243769
Rosendahl, Jonas ; Teich, Niels ; Kovacs, Peter ; Szmola, R. ; Blüher, Matthias ; Gress, Thomas M. ; Hoffmeister, Albrecht ; Keim, Volker ; Löhr, Matthias ; Mössner, Joachim ; Nickel, Renate ; Ockenga, Johann ; Pfützer, Roland ; Schulz, Hans Ulrich ; Stumvoll, Michael ; Wittenburg, Henning ; Sahin-Tóth, Miklós ; Witt, Heiko. / Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis. In: Pancreatology. 2010 ; Vol. 10, No. 2-3. pp. 243-249.
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