PT  - JOURNAL ARTICLE
AU  - Hirota, Masahiko
AU  - Ohmuraya, Masaki
AU  - Baba, Hideo
TI  - Genetic background of pancreatitis
AID  - 10.1136/pgmj.2006.050591
DP  - 2006 Dec 01
TA  - Postgraduate Medical Journal
PG  - 775--778
VI  - 82
IP  - 974
4099  - http://pmj.bmj.com/content/82/974/775.short
4100  - http://pmj.bmj.com/content/82/974/775.full
SO  - Postgrad Med J2006 Dec 01; 82
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.