Serine protease inhibitor kazal type 1 mutations and pancreatitis.
SPINKI is thought to play an important role in protecting the pancreas against excessive trypsinogen activation. SPINK1 mutations are associated with the development of acute and chronic pancreatitis and have been detected in all forms of chronic pancreatitis. The strong association of mutations in the PRSS1 gene and in the SPINKI gene with chronic pancreatitis supports the concept of intracellular trypsin activation as an initiating and extremely important step in the development of pancreatitis. The N34S mutation represents the most frequently observed pancreatitis-associated SPINKI variant. Because the SPINKI N34Smutation is very common in the general population, it is unlikely that this mutation alone can initiate the development of chronic pancreatitis. Thus, it rather appears that in most patients with SPINKI-associated chronic pancreatitis, this genetic variant acts as disease modifier or within a polygenic model with other yet unidentified genes or environmental co-factors. The possible interaction of mutations in the SPINK1 gene with other pancreatitis-associated susceptibility genes has to be investigated in future research efforts. The most promising candidate gene for such an interaction is the CFTR gene, because genetic alterations within the CFTRgene are also common in the general population and already have been associated with chronic pancreatitis.
Schneider
Alexander
A
Department of Medicine II (Gastroenterology, Hepatology and Infectious Diseases), University Hospital of Heidelberg at Mannheim, Theodor-Kutzer-Ufer 1-3 D-68135, Mannheim, Germany. alexander.schneider@med.ma.uni-heidelberg.de
D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002908:Chronic Disease; D006801:Humans; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics* / Q000378:metabolism*; D014359:Trypsin Inhibitor, Kazal Pancreatic
D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic