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

Rosendahl, J. and Witt, H. and Szmola, R. and Bhatia, E. and Ozsvári, B. and Landt, O. and Schulz, H. U. and Gress, T. M. and Pfützer, R. and Löhr, M. and Kovacs, P. and Blüher, M. and Stumvoll, M. and Choudhuri, G. and Hegyi, P. and te Morsche, R. H. and Drenth, J. P. and Truninger, K. and Macek, M. and Puhl, G. and Witt, U. and Schmidt, H. and Büning, C. and Ockenga, J. and Kage, A. and Groneberg, D. A. and Nickel, R. and Berg, T. and Wiedenmann, B. and Bödeker, H. and Keim, V. and Mössner, J. and Teich, N. and Sahin-Tóth, M.. (2008) Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nature genetics, Vol. 40, H. 1. pp. 78-82.

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Official URL: http://edoc.unibas.ch/dok/A6006129

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
UniBasel Contributors:Truninger, Kaspar Ulrich
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publ
ISSN:1061-4036
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:25

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