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

Nature Genetics

Volumn 40, Issue 1, 2008, Pages 78-82

  Rosendahl, Jonas ^a   Witt, Heiko ^b   Szmola, Richárd ^c   Bhatia, Eesh ^d   Ózsvári, Béla ^c,e   Landt, Olfert ^f   Schulz, Hans Ulrich ^g   Gress, Thomas M ^h   Pfützer, Roland ⁱ   Löhr, Matthias ^j   Kovacs, Peter ^k   Blüher, Matthias ^a   Stumvoll, Michael ^a   Choudhuri, Gourdas ^d   Hegyi, Péter ^e   Te Morsche, René H M ^l   Drenth, Joost P H ^l   Truninger, Kaspar ^m   Macek Jr , Milan ⁿ   Puhl, Gero ^b   Witt, Ulrike ^b   Schmidt, Hartmut ^o   Büning, Carsten ^b   Ockenga, Johann ^b   Kage, Andreas ^b   Groneberg, David Alexander ^b   Nickel, Renate ^b   Berg, Thomas ^b   Wiedenmann, Bertram ^b   Bödeker, Hans ^a   Keim, Volker ^a   Mössner, Joachim ^a   Teich, Niels ^a   Sahin Tóth, Miklós ^c   more..

^a UNIVERSITY OF LEIPZIG   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c BOSTON UNIVERSITY   (United States)

^d SANJAY GANDHI POSTGRADUATE INSTITUTE OF MEDICAL SCIENCES   (India)

^e UNIVERSITY OF SZEGED   (Hungary)

^f TIB MOLBIOL   (Germany)

^g OTTO VON GUERICKE UNIVERSITY   (Germany)

^h PHILIPPS UNIVERSITY MARBURG   (Germany)

ⁱ UNIVERSITY OF HEIDELBERG   (Germany)

^j KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^k UNIVERSITY HOSPITAL LEIPZIG   (Germany)

^l RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^m UNIVERSITY OF BERN   (Switzerland)

ⁿ UNIVERSITY HOSPITAL MOTOL   (Czech Republic)

^o UNIVERSITY HOSPITAL MÜNSTER   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CHYMOTRYPSIN A; CHYMOTRYPSIN C; UNCLASSIFIED DRUG;

ALCOHOL LIVER DISEASE; ARTICLE; CHRONIC PANCREATITIS; CONTROLLED STUDY; FEMALE; GENE ACTIVITY; GENE DELETION; GENE FUNCTION; GENETIC PREDISPOSITION; GENETIC RISK; GENETIC VARIABILITY; GERMANY; HUMAN; HUMAN CELL; INDIAN; MAJOR CLINICAL STUDY; MALE; MUTATION; NUCLEOTIDE SEQUENCE; PANCREAS SECRETION; PRIORITY JOURNAL;

CELL LINE; CHYMOTRYPSIN; GERMANY; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; PANCREATITIS, ALCOHOLIC; PANCREATITIS, CHRONIC;

EID: 37549072225     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.2007.44     Document Type: Article

References (18)

1. Whitcomb, D.C. et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat. Genet. 14, 141-145 (1996).
2. Gorry, M.C. et al. Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis. Gastroenterology 113, 1063-1068 (1997).
3. Teich, N., Mössner, J. & Keim, V. Mutations of the cationic trypsinogen in hereditary pancreatitis. Hum. Mutat. 12, 39-43 (1998).
4. Witt, H., Luck, W. & Becker, M. A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis. Gastroenterology 117, 7-10 (1999).
5. Le Maréchal, C. et al. Hereditary pancreatitis caused by triplication of the trypsinogen locus. Nat. Genet. 38, 1372-1374 (2006).
6. Teich, N. et al. Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis. Hum. Mutat. 27, 721-730 (2006).
7. Sahin-Tóth, M. Biochemical models of hereditary pancreatitis. Endocrinol. Metab. Clin. North Am. 35, 303-312 (2006).
8. Witt, H. et al. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat. Genet. 25, 213-216 (2000).
9. Pfützer, R.H. et al. PSTI/SPINK1 polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis. Gastroenterology 119, 615-623 (2000).
10. Witt, H. et al. Mutation in the SPINK1 trypsin inhibitor gene, alcohol use, and chronic pancreatitis. J. Am. Med. Assoc. 285, 2716-2717 (2001).
11. Chandak, G.R. et al. Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis. J. Med. Genet. 39, 347-351 (2002).
12. Bhatia, E. et al. Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations. Gastroenterology 123, 1020-1025 (2002).
13. Schneider, A. et al. SPINK1/PSTI mutations are associated with tropical pancreatitis and type II diabetes mellitus in Bangladesh. Gastroenterology 123, 1026-1030 (2002).
14. Király, O., Wartmann, T. & Sahin-Tóth, M. Missense mutations in pancreatic secretory trypsin inhibitor (SPINK1) cause intracellular retention and degradation. Gut 56, 1433-1438 (2007).
15. Boulling, A. et al. Functional analysis of pancreatitis-associated missense mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. Eur. J. Hum. Genet. 15, 936-942 (2007).
16. Witt, H. et al. A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis. Nat. Genet. 38, 668-673 (2006).
17. Szmola, R. & Sahin-Tóth, M. Chymotrypsin C (caldecrin) promotes degradation of human cationic trypsin: identity with Rinderknecht's enzyme Y. Proc. Natl. Acad. Sci. USA 104, 11227-11232 (2007).
18. Jessop, N.W. & Hay, R.J. Characteristics of two rat pancreatic exocrine cell lines derived from transplantable tumors. In Vitro 16, 212 (1980).