It has been established that mutations in the genes related to the activation and inactivation of trypsin(ogen) such as PRSS1, serine protease inhibitor Kazal type 1 (SPINK1) and chymotrypsin C (CTRC) genes are associated with pancreatitis.
Trypsin-encoding <i>PRSS1-PRSS2</i> variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report.
Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis.
The aim of our study was to describe the prevalence, characteristics, and outcomes of children with acute recurrent (ARP) or chronic (CP) pancreatitis with or without mutations in PRSS1, CFTR or SPINK1.
After exclusion of patients with trypsinogen (PRSS1) mutations, cystic fibrosis, or pulmonary disease, and with known risk factors for pancreatitis 67 patients with idiopathic chronic pancreatitis (ICP) from northwest Germany and 60 geographically and ethnically matched controls were recruited.
Four of 25 patients with pHPT and pancreatitis carried the N34S missense mutation in the SPINK1 gene (16%), while all 50 controls (pHPT without pancreatitis) showed no mutation in SPINK1 or PRSS1 genes (P < 0.05 vs controls, P < 0.001 vs general population).
The strong association of mutations in the PRSS1 gene and in the SPINK1 gene with chronic pancreatitis supports the concept of intracellular trypsin activation as an initiating and extremely important step in the development of pancreatitis.
this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis.
By analogy with the known PRSS1 mutations, predisposition to pancreatitis by some of them, particularly the V123M autolysis cleavage site mutation, is suspected.
Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk.
We found the heterozygous G62C mutation in n = 3/80 patients (n = 2/52 patients from different families, 3.8%) with familial pancreatitis without PRSS1 mutation and in n = 3/126 patients (2.4%) with sporadic pancreatitis.
Human studies suggest that PRSS1 and SPINK1 mutation increase the pancreas' susceptibility to alcohol-associated pancreatitis, and that tobacco smoking, and some factors, affect disease progression.
We collected clinical data for 210 patients with recurrent acute or chronic pancreatitis, and examined mutations of the cationic trypsinogen (CT) gene in 57 patients with a family history of pancreatitis or with early-onset idiopathic recurrent acute or chronic pancreatitis (40 years of age or younger).
Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.
PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768).
Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.
According to the <i>Cathepsin B</i> hypothesis, mutated CTSB can lead to premature intracellular activation of trypsinogen, a key regulatory mechanism in pancreatitis.
Two hundred sixty patients were screened for the most frequent mutations in major pancreatitis-associated genes, such as cationic trypsinogen/serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), and cystic fibrosis transmembrane conductance regulator gene (CFTR).
Antagonists at CB1- and CB2-receptors were effective in reversing HU210-induced antinociception, whereas a combination of CB1- and CB2-antagonists was required to block the anti-inflammatory effects of HU210 in pancreatitis.