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


CONCLUSIONS
The results classify E32del mesotrypsinogen as a frequent polymorphic variant, which is not associated with chronic alcoholic pancreatitis.
Nemoda
Zsófia
Z
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, MA, USA.
Teich
Niels
N
Hugenberg
Christin
C
Sahin-Tóth
Miklós
M
D002908:Chronic Disease; D004789:Enzyme Activation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D019512:Pancreatitis, Alcoholic / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014357:Trypsin / Q000235:genetics* / Q000378:metabolism
C040749:PRSS3 protein, human; D014357:Trypsin