Advances in the etiology of chronic pancreatitis.
In the past, chronic pancreatitis has been regarded as a fairly uniform and largely untreatable disorder that most commonly affects patients who both lack gainful employment or adequate insurance coverage and have a tendency to smoke and drink. Large clinical trials suggest that this perception is not only misguided and discriminatory but also not based on facts. We forgot that the perception of chronic liver disease was similar before World War II, and just like liver cirrhosis the fibrosis and cirrhosis of the pancreas--i.e. chronic pancreatitis--is the end result of a range of environmental, inflammatory, infectious and genetic disorders. A growing number of these have only recently been recognized as a distinct entity and several of which are becoming truly treatable. A large proportion of the risk for developing pancreatitis is conveyed by genetic risk factors, and we estimate that less than half of those have been identified so far. The same holds true for protective factors that can prevent pancreatitis, even in the face of excessive alcohol abuse. Various gene mutations and polymorphisms appear to determine an individual's susceptibility for developing pancreatic disease, for the severity of the disease, and for the disease progression. The spectrum of genotype/phenotype associations ranges from straightforward autosomal dominant traits with near-complete penetrance, as for the most common mutations in the cationic trypsinogen gene (PRSS1), to moderate risks factors without mendelian inheritance patterns, as for SPINK1 and CFTR mutations, to very subtle risk associations and disease modifiers that can only be identified in large cohort studies, as for the chymotrypsin C, calcium-sensing receptor and the anionic trypsin (PRSS2) mutations. Only a better understanding of the disease mechanisms that underlie these changes will make an individualized therapy of pancreatic disorders a realistic option.
Lerch
Markus M
MM
Department of Medicine A, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
Mayerle
Julia
J
Aghdassi
Ali A
AA
Budde
Christoph
C
Nitsche
Claudia
C
Sauter
Gabriele
G
Persike
Maria
M
Günther
Annett
A
Simon
Peter
P
Weiss
F Ulrich
FU
D000818:Animals; D006801:Humans; D009154:Mutation / Q000235:genetics; D050500:Pancreatitis, Chronic / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D011506:Proteins / Q000235:genetics
D011506:Proteins