Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis

Heiko Witt, Werner Luck, Hans Christian Hennies, Martin Claßen, Andreas Kage, Ulrich Laß, Olfert Landt, Michael Becker

Research output: Contribution to journalLetter

739 Citations (Scopus)

Abstract

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor. Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.

Original languageEnglish
Pages (from-to)213-216
Number of pages4
JournalNature Genetics
Volume25
Issue number2
DOIs
Publication statusPublished - 1 Jun 2000
Externally publishedYes

Fingerprint

Serine Proteinase Inhibitors
Chronic Pancreatitis
Mutation
Genes
Trypsinogen
Trypsin Inhibitors
Missense Mutation
Codon
Trypsin
Pancreas
Peptide Hydrolases
Inflammation

Cite this

Witt, Heiko ; Luck, Werner ; Hennies, Hans Christian ; Claßen, Martin ; Kage, Andreas ; Laß, Ulrich ; Landt, Olfert ; Becker, Michael. / Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. In: Nature Genetics. 2000 ; Vol. 25, No. 2. pp. 213-216.
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abstract = "Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor. Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23{\%} of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.",
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Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. / Witt, Heiko; Luck, Werner; Hennies, Hans Christian; Claßen, Martin; Kage, Andreas; Laß, Ulrich; Landt, Olfert; Becker, Michael.

In: Nature Genetics, Vol. 25, No. 2, 01.06.2000, p. 213-216.

Research output: Contribution to journalLetter

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AU - Witt, Heiko

AU - Luck, Werner

AU - Hennies, Hans Christian

AU - Claßen, Martin

AU - Kage, Andreas

AU - Laß, Ulrich

AU - Landt, Olfert

AU - Becker, Michael

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