ATL>Mutational screening of patients with nonalcoholic chronic pancreatitis: identification of further trypsinogen variants

Teich, Niels; Bauer, Nadine; Mössner, Joachim; Keim, Volker
February 2002
American Journal of Gastroenterology;Feb2002, Vol. 97 Issue 2, p341
Academic Journal
OBJECTIVES:Mutations of the cationic trypsinogen (CT) and the serine protease inhibitor, Kazal type 1 (SPINK 1) are associated with chronic pancreatitis. After mutational screening of a cohort of patients with nonalcoholic chronic pancreatitis, we report three novel variants of the trypsinogen molecule and the clinical characteristics of the carriers.METHODS:The coding region of the exon 2 and 3 of the CT gene of 523 patients with chronic nonalcoholic pancreatitis (108 patients with suspected hereditary pancreatitis (HP) and 415 patients with “idiopathic” pancreatitis [IP]) and 82 controls was analyzed after polymerase chain reaction amplification. Clinical characteristics were obtained by questioning the patients and their relatives and physicians. HP was suspected when two members of a family had chronic pancreatitis. A restriction digestion was used to analyze the N34S mutation SPINK 1.RESULTS:The mutation R122H of the cationic trypsinogen was found in 21 index patients, N29I in six index patients, and A16V and D22G in one index patient, all from HP families. The N34S mutation of SPINK 1 was found in two index patients with a family history of HP. In three patients, the novel point mutations L104P, R116C, and C139F of the cationic trypsinogen were found. A clear autosomally dominant inheritance of chronic pancreatitis was not present in these families. In 75 index patients from HP families (69.4%), no mutation could be found. The SPINK 1-mutation N34S was detected in only one patient carrying a CT mutation, and was found in 68 (16.4%) of patients with IP.CONCLUSIONS:The R122H and N29I mutations of CT are the most common disease-associated mutations in HP; the N34S mutation of SPINK 1 is the most frequent genetic risk factor associated with IP. The CT gene carries several variations that could be associated with chronic pancreatitis. To avoid overestimating the pathogenetic impact of novel trypsinogen variants, a detailed clinical characterization of all patients with early onset chronic pancreatitis is mandatory.


Related Articles

  • The Medicinal Chemistry of Protease Inhibitors. Diederich, Wibke E.; Wegscheid-Gerlach, Christof // Current Topics in Medicinal Chemistry;Feb2010, Vol. 10 Issue 3, p231 

    The article discusses various reports published within the issue including one about the advances and new perspectives of proteasome inhibitors and another on the field of factor Xa.

  • Unraveling Sub-Site Specificities of Peptidic Serine Protease Inhibitors by Substitutional and Structural Analysis. Höhne, Wolfgang; Hilpert, Kai // Protein & Peptide Letters;Jul2005, Vol. 12 Issue 5, p449 

    The interaction of peptidic inhibitors with serine proteases is investigated using peptide spot synthesis on cellulose sheets. This method permits a highly parallel analysis of subsite specificities and an optimization of peptidic inhibitors towards higher affinity and specificity for a given...

  • Plant Serine Proteinase Inhibitors. Christeller, John; Laing, William // Protein & Peptide Letters;Jul2005, Vol. 12 Issue 5, p439 

    Evidence that establishes the mechanism of the classes of plant proteinase inhibitors (PIs) is evaluated. Of the eight classes of PIs, six are unique to plants. Except for plant serpins, there is evidence that PIs from all other classes form tight binding complexes with their target proteinases,...

  • The Role Played by Serine Proteases in the Development and Worsening of Vascular Complications in Type 1 Diabetes Mellitus. Finotti, Paola // Current Diabetes Reviews;2006, Vol. 2 Issue 3, p295 

    Much attention has been given to the role played by serine proteases in the development and worsening of vascular complications in Type 1 diabetes mellitus. A generalized increase in proteolytic activity, either due to a true increase in concentration of specific proteases or defects of their...

  • Atlantic Cod Trypsin Y--Member of a Novel Trypsin Group. Spilliaert, R�mi; Gudmundsd�ttir, �g�sta // Marine Biotechnology;1999, Vol. 1 Issue 6, p598 

    A unique trypsinogen complementary DNA has been isolated from an Atlantic cod (Gadus morhua) cDNA library. Its predicted amino acid sequence contains 249 residues with a putative polypeptide of 227 residues. The distinctive features of this polypeptide, referred to as trypsin Y, are its low...

  • Novel Role of the Serine Protease Inhibitor Elafin in Gluten-Related Disorders. Galipeau, Heather J; Wiepjes, Michelle; Motta, Jean-Paul; Schulz, Jessica D; Jury, Jennifer; Natividad, Jane M; Pinto-Sanchez, Ines; Sinclair, Daniel; Rousset, Perrine; Martin-Rosique, Rebeca; Bermudez-Humaran, Luis; Leroux, Jean Christophe; Murray, Joseph A; Smecuol, Edgardo; Bai, Julio C; Vergnolle, Nathalie; Langella, Philippe; Verdu, Elena F // American Journal of Gastroenterology;May2014, Vol. 109 Issue 5, p748 

    OBJECTIVES:Elafin, an endogenous serine protease inhibitor, modulates colonic inflammation. We investigated the role of elafin in celiac disease (CD) using human small intestinal tissues and in vitro assays of gliadin deamidation. We also investigated the potential beneficial effects of elafin...

  • Structure-Activity Relationship Within the Serine Protease Inhibitors of the Pacifastin Family. Kellenberger, Christine; Roussel, Alain // Protein & Peptide Letters;Jul2005, Vol. 12 Issue 5, p409 

    The members of the Pacifastin family are serine protease inhibitors found in insects and crustacean. They are either small inhibitors (made of one consensus cysteine-rich motif) or proteins (4-9 motifs). Some of these inhibitors are characterized by a species selectivity for the trypsin...

  • Recent Developments in the Design of Mechanism-based and Alternate Substrate Inhibitors of Serine Proteases. Zhong, Jiaying; Groutas, William C. // Current Topics in Medicinal Chemistry;Aug2004, Vol. 4 Issue 12, p1203 

    A wide range of human diseases are associated with the aberrant activity of mammalian, viral, bacterial or parasitic proteases. These include members of all four classes of proteases, namely, serine, cysteine, aspartic and metalloproteases. The involvement of proteases in disease states has...

  • Kallikrein-binding protein inhibits retinal neovascularization and decreases vascular leakage G. Gao et al.: Anti-angiogenic activity of KBP. Gao, G.; Shao, C.; Zhang, S. X.; Dudley, A.; Fant, J.; Ma, J.-X. // Diabetologia;May2003, Vol. 46 Issue 5, p689 

    Aims/hypothesis. Kallikrein-binding protein (KBP) is a serine proteinase inhibitor (serpin). It specifically binds to tissue kallikrein and inhibits kallikrein activity. Our study was designed to test its effects on retinal neovascularization and vascular permeability. Methods. Endothelial cell...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics