title: Human cationic trypsinogen but not serine peptidase inhibitor, Kazal type 1 variants increase the risk of type 1 autoimmune pancreatitis.
abstract: OBJECTIVE
  Autoimmune pancreatitis (AIP) is a distinct disease entity. Whether the genes involved in pancreatic acinar cell injury, cationic trypsinogen gene (protease, serine, 1 [trypsin 1] [PRSS1]) and the pancreatic secretory trypsin inhibitor gene (serine peptidase inhibitor, Kazal type 1 [SPINK1]), are associated with AIP remains to be explored.
  
  
  METHODS
  Genetic analyses of PRSS1 variants (exon 2 and 3) and SPINK1 variants (exon 1, 2, and 3) including the intronic areas in 118 patients with AIP and 200 control subjects were performed by direct DNA sequencing. Clinical features including imaging, histology, serology, response to steroid, and extra-pancreatic organ involvement in AIP patients with and without variants were compared.
  
  
  RESULTS
  A total of 19 PRSS1 variants and one SPINK1 variant were identified in 20 (16.9%) out of 118 AIP patients. They included one K92N, nine R116C, seven T137M, one C139S, and one C139F of PRSS1 and one 2(IVS3 + 2) of SPINK1. No PRSS1 or SPINK1 variant was identified in the control group. Patients with PRSS1 variants had an increased risk of AIP with odds ratio 22.37 (95% confidence interval: 2.96-168.8, P = 0.003) and higher frequency of serum IgG4 above 280 mg/dL. Using immunosuppressive agent and PRSS1 variant were predictors of less disease relapse in univariate analysis. Presence of PRSS1 variants was the only negative predictor for disease relapse in multivariate analysis.
  
  
  CONCLUSIONS
  We found a significantly higher frequency of PRSS1 variants in AIP patients than in geographically and ethnically matched control subjects. PRSS1 variants are associated with less disease relapse in AIP.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Chang
authors.forename: I-Shiow
authors.initials: IS
authors.lastname: Jan
authors.forename: Po-Chin
authors.initials: PC
authors.lastname: Liang
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Tien
authors.forename: Jau-Min
authors.initials: JM
authors.lastname: Wong
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chang
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics*; D012306:Risk; D014357:Trypsin / Q000235:genetics*; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; C489303:PRSS1 protein, human; D014357:Trypsin
keywords: PRSS1; SPINK1; autoimmune pancreatitis; trypsinogen