Human cationic trypsinogen but not serine peptidase inhibitor, Kazal type 1 variants increase the risk of type 1 autoimmune pancreatitis

• Published in: Journal of gastroenterology and hepatology Vol. 29; no. 12; pp. 2038 - 2042
• Main Authors: Chang, Ming-Chu, Jan, I-Shiow, Liang, Po-Chin, Jeng, Yung-Ming, Yang, Ching-Yao, Tien, Yu-Wen, Wong, Jau-Min, Chang, Yu-Ting
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.12.2014
• Subjects: Adult; Autoimmune Diseases - genetics; autoimmune pancreatitis; Carrier Proteins - genetics; Exons - genetics; Female; Genetic Variation; Humans; Male; Middle Aged; Pancreatitis - genetics; PRSS1; Risk; SPINK1; Trypsin - genetics; Trypsin Inhibitor, Kazal Pancreatic; trypsinogen; autoimmune pancreatitis; trypsinogen; PRSS1; SPINK1
• ISSN: 0815-9319; 1440-1746; 1440-1746
• DOI: 10.1111/jgh.12649

Background and Aim 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.