The frequency of PD was higher in patients with CFTR gene-associated pancreatitis as compared with those with idiopathic and alcoholic pancreatitis (P<0.0001) and with those with SPINK1 and PRSS1 gene-associated pancreatitis (P<0.02).
This problematic trend is notably illustrated by two recent studies that classified the p.A121TPRSS1 variant as pancreatitis associated, in large part owing to its intimate proximity to arginine-122, the residue affected by the disease causing p.R122H mutation.
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.
The understanding of genetic risk factors for chronic pancreatitis increased in the last decade with the discovery of mutations in the cationic trypsinogen gene (PRSS1).
Mice that express PRSS1<sup>R122H</sup> developed more severe pancreatitis after ethanol feeding or a high-fat diet than mice that express PRSS1 or control mice.
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.
Inclusion criteria were the presence of mutation in the cationic trypsingen gene (PRSS1 gene), or chronic pancreatitis in at least two first-degree relatives, or three second-degree relatives, in the absence of precipitating factors for pancreatitis.
A model of interactions between environmental triggers of pancreatic inflammation and disease susceptibility or modifying genes (including PRSS1, SPINK1 and CFTR) provides a framework within which to understand disease pathogenesis.
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.
Relative expression of: (a) the PRSS1 R122 and H122 alleles; and (b) the PRSS1 and SPINK1 genes in pancreatitis were determined using complementary methods.
We analyzed 381 patients with a primary diagnosis of chronic or recurrent pancreatitis using the Ambry Test: Pancreatitis to obtain comprehensive genetic information for the CFTR, SPINK1, and PRSS1 genes.
Previous studies have shown an association of variants in trypsin-associated genes, such as cationic trypsinogen (PRSS1) and serine protease inhibitor, Kazal type-1 (SPINK1) with pancreatitis.