Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis

• Published in: Journal of medical genetics 2002-05, Vol.39 (5), p.347-351
• Main Authors: Chandak, G R, Idris, M M, Reddy, D N, Bhaskar, S, Sriram, P V J, Singh, L
• Format: Article
• Language: English
• Subjects: 1 (trypsin 1); Adult; Alcoholism; Base Sequence; Biological and medical sciences; Calcinosis - complications; Calcinosis - diagnosis; Calcinosis - genetics; cationic trypsinogen gene; CFTR; Chronic Disease; cystic fibrosis transmembrane regulator; Diabetes Complications; DNA Mutational Analysis; endoscopic retrograde cholangio-pancreaticography; ERCP; FCPD; Female; fibrocalculous pancreatic diabetes; Gastroenterology. Liver. Pancreas. Abdomen; Genes; Genetic Predisposition to Disease; glucose tolerance test; GTT; hereditary pancreatitis; Humans; ICP; idiopathic chronic pancreatitis; Kazal type I; Letter to JMG; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Mutation; Other diseases. Semiology; pancreatic secretory trypsin inhibitor; pancreatic secretory trypsin inhibitor gene; Pancreatitis - complications; Pancreatitis - diagnosis; Pancreatitis - genetics; Pancreatitis - pathology; Phenotype; protease; PRSS1; PSTI; serine; serine protease inhibitor; SPINK1; Studies; TCP; tropical calcific pancreatitis; Trypsin; Trypsin Inhibitor, Kazal Pancreatic - genetics; Trypsinogen - genetics
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.39.5.347

A genetic basis was reported in 1996 by familial linkage analysis 3- 5 and confirmed by detection of missense mutations, namely R122H and N29I, in the cationic trypsinogen gene (PRSS1) in hereditary pancreatitis (HP) patients. 6, 7 HP is a relatively rare autosomal dominant disorder where typical acute attacks in childhood and frequent progression to chronic pancreatitis are seen to occur in two or more subjects or generations. Pancreatic secretory trypsin inhibitor (PSTI/SPINK1) is a potent protease inhibitor and thought to be a major protective mechanism preventing inappropriate activation of pancreatic digestive enzyme cascade by inhibiting up to 20% of potential trypsin activity. 12 The human SPINK1 gene on chromosome 5 is approximately 7.5 kb long with four exons and codes for a product of 79 amino acids including a signal peptide of 23 amino acids. 13 Since the inhibitor molecule provides the first line of defence against prematurely activated trypsinogen within the pancreas, it has recently attracted attention as a possible cause of chronic pancreatitis.