PRSS1_p.Leu81Met mutation results in autoimmune pancreatitis.

Abstract

AIM:

To describe protease serine 1 (PRSS1) gene mutations in patients with autoimmune pancreatitis (AIP) and the clinical features of AIP.

METHODS:

Fourteen patients with AIP, 56 with other chronic pancreatitis, 254 with pancreatic cancer and 120 normal controls were studied. The mutations and polymorphisms of four genes involved with pancreatitis or pancreatic cancer, PRSS1, SPINK1, CFTR and MEN1, were sequenced. The pathogenic mechanism of AIP was investigated by comparing the wild-type expression system with the p.81Leu→Met mutant expression system.

RESULTS:

Two novel mutations (p.81Leu→Met and p.91Ala→Ala) were found in PRSS1 gene from four patients with AIP. PRSS1_p.81Leu→Met mutation led to a trypsin display reduction (76.2%) combined with phenyl agarose (Ca(2+) induced failure). Moreover, the ratio of trypsin/amylase in patients with AIP was higher than in the patients with pancreatic cancer and other pancreatitis. A large number of lymphocytes and plasma cells were found in the bile ducts accompanied by hyperplasia of myofibroblasts.

CONCLUSION:

Autoimmune pancreatitis may be related to PRSS1 gene mutations.

• Authors: Feng Gao, Yue-Ming Li, Guo-Lin Hong, Zhi-Feng Xu, Qi-Cai Liu, Qing-Liang He, Li-Qing Lin, Shao-Huang Weng
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 19 Issue 21 Pg. 3332-8 (Jun 07 2013) ISSN: 2219-2840 [Electronic] United States
• PMID: 23745036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Glucocorticoids
• Recombinant Proteins
• Amylases
• PRSS1 protein, human
• Trypsin
• Calcium

Topics

• Adult
• Aged
• Amylases (blood)
• Autoimmune Diseases (blood, diagnosis, drug therapy, enzymology, genetics)
• Biomarkers (blood)
• Biopsy
• Calcium (metabolism)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Glucocorticoids (therapeutic use)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Mutation
• Pancreatic Neoplasms (enzymology, genetics)
• Pancreatitis (blood, diagnosis, drug therapy, enzymology, genetics)
• Pancreatitis, Chronic (enzymology, genetics)
• Phenotype
• Recombinant Proteins (metabolism)
• Tomography, X-Ray Computed
• Trypsin (blood, genetics)