A total of 261 patients with AP (174 with a sentinel attack, and 87 with recurrent attacks) and healthy controls were genotyped for the p.R122H mutation in the PRSS1 gene, p.N34S and IVS3 + 2T > C variants in the SPINK1 gene, the p.G191R variant in the anionic trypsinogen gene, the p.E32del variant in the mesotrypsinogen (PRSS3) gene, and the -2518G > A variant in the monocyte chemoattractant protein-1 gene by polymerase chain reaction-restriction enzyme digestion and direct sequencing.
A total of 261 patients with AP (174 with a sentinel attack, and 87 with recurrent attacks) and healthy controls were genotyped for the p.R122H mutation in the PRSS1 gene, p.N34S and IVS3 + 2T > C variants in the SPINK1 gene, the p.G191R variant in the anionic trypsinogen gene, the p.E32del variant in the mesotrypsinogen (PRSS3) gene, and the -2518G > A variant in the monocyte chemoattractant protein-1 gene by polymerase chain reaction-restriction enzyme digestion and direct sequencing.
The p.G191R frequency was lower in patients with alcoholic (0.9%; p = 0.015; OR, 0.132; 95% CI, 0.022 to 0.779) and idiopathic (1.0%; p = 0.025; OR, 0.144; 95% CI, 0.025 to 0.851) chronic pancreatitis than that in healthy controls.
The p.G191R frequency was lower in patients with alcoholic (0.9%; p = 0.015; OR, 0.132; 95% CI, 0.022 to 0.779) and idiopathic (1.0%; p = 0.025; OR, 0.144; 95% CI, 0.025 to 0.851) chronic pancreatitis than that in healthy controls.
These observations, which are complementary to the previous findings, provide further insights into the genetic mechanism and pathogenic role of the N21I mutation in HP.
The observations suggest that autocatalytic trypsinogen degradation may be an important defense mechanism against excessive trypsin generation in the pancreas, and trypsinogen stabilization by the Asn(21) --> Ile mutation plays a role in the pathogenesis of HP.
While rs62228256 was not validated as a risk factor (<i>P</i>=0.77), both rs13228878 (<i>P</i>=0.03) and rs10273639 (<i>P</i>=0.04) were. rs13228878 and rs10273639 are in high linkage disequilibrium (r<sup>2</sup>=0.94) and associated with elevated expression of the <i>PRSS1</i> gene, which encodes for trypsinogen, and are known risk variants for alcohol-associated and sporadic pancreatitis in adults.
A total of 261 patients with AP (174 with a sentinel attack, and 87 with recurrent attacks) and healthy controls were genotyped for the p.R122H mutation in the PRSS1 gene, p.N34S and IVS3 + 2T > C variants in the SPINK1 gene, the p.G191R variant in the anionic trypsinogen gene, the p.E32del variant in the mesotrypsinogen (PRSS3) gene, and the -2518G > A variant in the monocyte chemoattractant protein-1 gene by polymerase chain reaction-restriction enzyme digestion and direct sequencing.
A total of 261 patients with AP (174 with a sentinel attack, and 87 with recurrent attacks) and healthy controls were genotyped for the p.R122H mutation in the PRSS1 gene, p.N34S and IVS3 + 2T > C variants in the SPINK1 gene, the p.G191R variant in the anionic trypsinogen gene, the p.E32del variant in the mesotrypsinogen (PRSS3) gene, and the -2518G > A variant in the monocyte chemoattractant protein-1 gene by polymerase chain reaction-restriction enzyme digestion and direct sequencing.