RT Journal Article
SR Electronic
T1 Genetic background of pancreatitis
JF Postgraduate Medical Journal
JO Postgrad Med J
FD The Fellowship of Postgraduate Medicine
SP 775
OP 778
DO 10.1136/pgmj.2006.050591
VO 82
IS 974
A1 Hirota, Masahiko
A1 Ohmuraya, Masaki
A1 Baba, Hideo
YR 2006
UL http://pmj.bmj.com/content/82/974/775.abstract
AB Trypsin activity is properly suppressed by pancreatic secretory trypsin inhibitor (PSTI), which is also known as serine protease inhibitor Kazal type 1 (SPINK1), thereby preventing damage to pancreatic acinar cells as a first line of defence. However, if trypsin activation exceeds the capacity of PSTI/SPINK1, a subsequent cascade of events leads to the activation of various proteases that damage cells. Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis. From analyses of hereditary pancreatitis and the phenotype of PSTI/SPINK1 (Spink3) knockout mice, we showed that the imbalance of trypsin activation and its inhibition by PSTI/SPINK1 would lead to the development of pancreatitis.