Another common polymorphism of the CFTR gene has recently been implicated in the pathogenesis of idiopathic chronic pancreatitis, the 5T variant of the variable length polythymidine tract in intron 8 (the normal genotypes are 7T and 9T).
Nine out of 48 (19%) patients referred to a pancreatic clinic with a presumed diagnosis of idiopathic chronic pancreatitis have been shown to have mutations in the cationic trypsinogen gene (PRSSI), consistent with a previously unsuspected diagnosis of hereditary pancreatitis.
Among the known PRSS1 mutations, only the R122H was detected in a single subject and the A16V in two subjects in the cohort, strengthening that HP-associated PRSS1 mutations are rare in ICP.
We tested 39 patients with idiopathic chronic pancreatitis (mean age at diagnosis, 33 years) for common mutations of CFTR and of genes encoding a trypsin inhibitor (PSTI) and trypsinogen (PRSS1).
Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis.
Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis.
Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis.
Recently, an association between the mutation N34S in the pancreatic secretory trypsin inhibitor (SPINK1 or PSTI) gene and idiopathic chronic pancreatitis (ICP) was reported.
Identification of SPINK1 mutations in 12.2% of patients with adult alcoholic and idiopathic chronic pancreatitis suggests an important role for SPINK1 as a predisposing factor in adult chronic pancreatitis.
Since SPINK1 mutations in Europeans and North Americans are associated with idiopathic chronic pancreatitis that is phenotypically different from FCPD, we further conclude that mutated SPINK1 markedly increases the risk of developing a variety of pancreatic diseases possibly through a chronic elevation of active trypsin within the pancreas.
Ten patients were homozygous for N34S, SPINK1 mutations were most common in 'idiopathic' CP, whereas patients with 'hereditary' CP predominantly showed a PRSS1 mutation (R122H, N29I).
In the last few years, several genes have been identified as being associated with hereditary and idiopathic chronic pancreatitis (CP), i.e.PRSS1, CFTR and SPINK1.
In the last few years, several genes have been identified as being associated with hereditary and idiopathic chronic pancreatitis (CP), i.e.PRSS1, CFTR and SPINK1.
This article presents the existing data on SPINK1 mutations in idiopathic chronic pancreatitis, familial pancreatitis, hereditary pancreatitis and tropical pancreatitis.
These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the classification, diagnosis, and pathogenesis of pancreatitis.
This study examined a series of patients with ICP to determine the prevalence and role of mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI).
The authors investigated two functionally active tumor necrosis factor (TNF) promoter region polymorphisms at positions -238 and -308 and the entire coding region of the corresponding TNF receptor 1 (TNFR1) gene in 54 patients with hereditary, familial, and idiopathic chronic pancreatitis who were previously tested negative forcationic trypsinogen mutations by direct DNA sequencing.
The authors investigated two functionally active tumor necrosis factor (TNF) promoter region polymorphisms at positions -238 and -308 and the entire coding region of the corresponding TNF receptor 1 (TNFR1) gene in 54 patients with hereditary, familial, and idiopathic chronic pancreatitis who were previously tested negative for cationic trypsinogen mutations by direct DNA sequencing.
The authors investigated two functionally active tumor necrosis factor (TNF) promoter region polymorphisms at positions -238 and -308 and the entire coding region of the corresponding TNF receptor 1 (TNFR1) gene in 54 patients with hereditary, familial, and idiopathic chronic pancreatitis who were previously tested negative for cationic trypsinogen mutations by direct DNA sequencing.