Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen.

BACKGROUND/AIMS: Mesotrypsin is a minor pancreatic digestive enzyme that degrades dietary trypsin inhibitors in the gut. In this study, we tested the hypothesis that the E32del genetic variant of mesotrypsin might represent a risk factor for the development of chronic pancreatitis, as a result of enhanced degradation of pancreatic secretory trypsin inhibitor. METHODS: We screened 97 German patients with chronic pancreatitis of alcoholic etiology and 109 healthy controls for the presence of the E32del variant and characterized the biochemical properties of E32del mesotrypsinogen. RESULTS: Higher allele frequency of the E32del variant was detected in the control population (25.7 vs. 18.0%), but the difference was not significant (p = 0.062). Recombinant E32del mesotrypsin exhibited normal catalytic activity, characteristic inhibitor resistance and inability to activate pancreatic zymogens. Degradation of trypsin inhibitors was unaffected by the E32del genotype. Interestingly, mesotrypsinogen-E32del was biochemically distinguishable from mesotrypsinogen by its faster activation with bovine enterokinase, while activation by human enterokinase, trypsin or cathepsin B was unchanged. CONCLUSION: The results classify E32del mesotrypsinogen as a frequent polymorphic variant, which is not associated with chronic alcoholic pancreatitis.