title: PRSS1_p.Leu81Met mutation results in autoimmune pancreatitis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Autoimmune pancreatitis may be related to PRSS1 gene mutations.
authors.affiliation: Department of Pathology, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Li
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Hong
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Xu
authors.forename: Qi-Cai
authors.initials: QC
authors.lastname: Liu
authors.forename: Qing-Liang
authors.initials: QL
authors.lastname: He
authors.forename: Li-Qing
authors.initials: LQ
authors.lastname: Lin
authors.forename: Shao-Huang
authors.initials: SH
authors.lastname: Weng
mesh_terms: D000328:Adult; D000368:Aged; D000681:Amylases / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics; D010195:Pancreatitis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D050500:Pancreatitis, Chronic / Q000201:enzymology / Q000235:genetics; D010641:Phenotype; D011994:Recombinant Proteins / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D014357:Trypsin / Q000097:blood / Q000235:genetics*
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D011994:Recombinant Proteins; D000681:Amylases; C489303:PRSS1 protein, human; D014357:Trypsin; D002118:Calcium
keywords: Autoimmune pancreatitis; Molecular mechanism; PRSS1; p.81Leu→Met