2. Academic Validation
  3. Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis

Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis

  • Nat Genet. 2008 Jan;40(1):78-82. doi: 10.1038/ng.2007.44.
Jonas Rosendahl 1,  Heiko Witt,  Richárd Szmola,  Eesh Bhatia,  Béla Ozsvári,  Olfert Landt,  Hans-Ulrich Schulz,  Thomas M Gress,  Roland Pfützer,  Matthias Löhr,  Peter Kovacs,  Matthias Blüher,  Michael Stumvoll,  Gourdas Choudhuri,  Péter Hegyi,  René H M te Morsche,  Joost P H Drenth,  Kaspar Truninger,  Milan Macek Jr,  Gero Puhl,  Ulrike Witt,  Hartmut Schmidt,  Carsten Büning,  Johann Ockenga,  Andreas Kage,  David Alexander Groneberg,  Renate Nickel,  Thomas Berg,  Bertram Wiedenmann,  Hans Bödeker,  Volker Keim,  Joachim Mössner,  Niels Teich,  Miklós Sahin-Tóth
Affiliations

Affiliation

  • 1 Department of Gastroenterology and Hepatology, University of Leipzig, Philipp-Rosenthal-Strasse 27, 04103 Leipzig, Germany.
PMID: 18059268 DOI: 10.1038/ng.2007.44
Abstract

Chronic pancreatitis is a persistent inflammatory disease of the pancreas, in which the digestive protease trypsin has a fundamental pathogenetic role. Here we have analyzed the gene encoding the trypsin-degrading Enzyme chymotrypsin C (CTRC) in German subjects with idiopathic or hereditary chronic pancreatitis. Two alterations in this gene, p.R254W and p.K247_R254del, were significantly overrepresented in the pancreatitis group, being present in 30 of 901 (3.3%) affected individuals but only 21 of 2,804 (0.7%) controls (odds ratio (OR) = 4.6; confidence interval (CI) = 2.6-8.0; P = 1.3 x 10(-7)). A replication study identified these two variants in 10 of 348 (2.9%) individuals with alcoholic chronic pancreatitis but only 3 of 432 (0.7%) subjects with alcoholic liver disease (OR = 4.2; CI = 1.2-15.5; P = 0.02). CTRC variants were also found in 10 of 71 (14.1%) Indian subjects with tropical pancreatitis but only 1 of 84 (1.2%) healthy controls (OR = 13.6; CI = 1.7-109.2; P = 0.0028). Functional analysis of the CTRC variants showed impaired activity and/or reduced secretion. The results indicate that loss-of-function alterations in CTRC predispose to pancreatitis by diminishing its protective trypsin-degrading activity.

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