Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.
We investigated 78 patients with hereditary and familial pancreatitis and 62 patients with sporadic pancreatitis that were tested negative forcationic trypsinogen gene mutations, and 73 controls.
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.
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).
Having found a nonsense mutation (c.111C>A; Y37X) and a splicing mutation (IVS2+1G>A) in the cationic trypsinogen gene (protease, serine, 1; PRSS1) in alcoholics without the development of CP, but not in alcoholics with CP and patients with hereditary or idiopathic CP, we propose that while "gain of function" mutations in the PRSS1 gene predispose one to pancreatitis, "loss of function" mutations in the gene may protect one against the disease.
Having found a nonsense mutation (c.111C>A; Y37X) and a splicing mutation (IVS2+1G>A) in the cationic trypsinogen gene (protease, serine, 1; PRSS1) in alcoholics without the development of CP, but not in alcoholics with CP and patients with hereditary or idiopathic CP, we propose that while "gain of function" mutations in the PRSS1 gene predispose one to pancreatitis, "loss of function" mutations in the gene may protect one against the disease.
In contrast to previous animal models exhibiting altered severity of pancreatitis, Itmap1 deficiency results in impaired activation of trypsin, an enzyme believed critical for initiating a cascade of digestive zymogen activation during pancreatitis.
Over the past 5 years, several gain-of-function missense mutations in the human cationic trypsinogen gene (PRSS1, OMIM 276000) have been associated with hereditary and/or sporadic pancreatitis.
By analogy with the known PRSS1 mutations, predisposition to pancreatitis by some of them, particularly the V123M autolysis cleavage site mutation, is suspected.
We performed sequence analysis of the cationic trypsinogen-coding region in 46 alcohol-related pancreatitis patients and 16 patients with pancreatitis due to causes other than alcohol.
A review of the ongoing hereditary pancreatitis study of the Midwest Multicenter Pancreatic Study Group suggests that the risk of pancreatic cancer is related to long-standing pancreatitis rather than to the cationic trypsinogen mutations.
Unlike in patients with hereditary pancreatitis, we found a lack of the R117H mutation in the cationic trypsinogen gene in all patients with tropical pancreatitis from Bangladesh.
We recently identified a single R117H mutation in the cationic trypsinogen gene in several kindreds with an inherited form of acute and chronic pancreatitis (HP1), providing strong evidence that trypsin plays a central role in premature zymogen activation and pancreatitis.
Finally, in rat pancreatic acinar cells, CB1- and CB2-receptors, expressed both in basal conditions and after CK-induced pancreatitis but inactive on amylase secretion, have an unknown role both in physiological and pathological conditions.