Mutational analysis of the gene encoding the zymogen granule membrane glycoprotein 2 (GP2) in patients with chronic pancreatitis

Heiko Witt, Jonas Rosendahl, René H.M. Te Morsche, Sundaresan Santhosh, Ashok Chacko, Hans Ulrich Schulz, Olfert Landt, Niels Teich, Volker Keim, Joachim Mössner, Thomas M. Gress, Johann Ockenga, Hartmut Schmidt, Peter Kovacs, Matthias Blüher, Michael Stumvoll, Andreas Kage, David Alexander Groneberg, Jan B.M.J. Jansen, Renate NickelJoost P.H. Drenth

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

4 Zitate (Scopus)

Abstract

Objectives: Premature activation of pancreatic digestive enzymes is considered as a major factor in the pathogenesis of pancreatitis. Genetic alterations of different pancreatic zymogens or their inhibitors have been associated with chronic pancreatitis (CP). Methods: We sequenced all 12 GP2 exons in 380 German CP patients and in 182 German control subjects. In addition, we analyzed exon 3 of GP2 in 803 further CP patients and 1780 controls originating from Germany, the Netherlands, and India by targeted DNA sequencing. Results: We detected 12 nonsynonymous and 6 synonymous exonic variants. All nonsynonymous changes with exception of c.220C>T (p.R74X) and c.502-503delG (p.G168fsX174) in exon 3 and c.541C>T (p.R181X) in exon 4 were missense mutations and predominantly located in exon 3. All nonsynonymous variants were found in single cases only, with exception of 2 alterations, c.355A>G (p.M119V) and c.409G>A (p. A137T), both located in exon 3. To elucidate the role of these 2 exon 3 variants, we investigated additional patients and controls. The frequency of these variants was similar between patients and controls regardless of ethnic background or cause of CP. Conclusions: Our data suggest that GP2 alterations do not alter the risk for the development of CP.

OriginalspracheEnglisch
Seiten (von - bis)188-192
Seitenumfang5
FachzeitschriftPancreas
Jahrgang39
Ausgabenummer2
DOIs
PublikationsstatusVeröffentlicht - März 2010

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