Chang Ming-Chu, Jan I-Shiow, Liang Po-Chin, Jeng Yung-Ming, Yang Ching-Yao, Tien Yu-Wen, Wong Jau-Min, Chang Yu-Ting
Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Gastroenterol Hepatol. 2014 Dec;29(12):2038-42. doi: 10.1111/jgh.12649.
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.
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.
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.
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.
自身免疫性胰腺炎（AIP）是一种独特的疾病实体。胰腺腺泡细胞损伤相关基因，即阳离子胰蛋白酶原基因（蛋白酶，丝氨酸，1 [胰蛋白酶1] [PRSS1]）和胰腺分泌性胰蛋白酶抑制剂基因（丝氨酸蛋白酶抑制剂，Kazal 型1 [SPINK1]）是否与AIP相关仍有待探索。
通过直接DNA测序对118例AIP患者和200例对照者进行PRSS1变异体（外显子2和3）和SPINK1变异体（外显子1、2和3）包括内含子区域的基因分析。比较有或无变异体的AIP患者的临床特征，包括影像学、组织学、血清学、对类固醇的反应以及胰腺外器官受累情况。
在118例AIP患者中的20例（16.9%）共鉴定出19种PRSS1变异体和1种SPINK1变异体。它们包括PRSS1的1个K92N、9个R116C、7个T137M、1个C139S和1个C139F以及SPINK1的1个2（IVS3 + 2）。在对照组中未鉴定出PRSS1或SPINK1变异体。携带PRSS1变异体的患者患AIP的风险增加，优势比为22.37（95%置信区间：2.96 - 168.8，P = 0.003），血清IgG4高于280mg/dL的频率更高。在单因素分析中，使用免疫抑制剂和PRSS1变异体是疾病复发较少的预测因素。在多因素分析中，PRSS1变异体的存在是疾病复发的唯一负性预测因素。
我们发现AIP患者中PRSS1变异体的频率显著高于地理和种族匹配的对照者。PRSS1变异体与AIP患者疾病复发较少相关。
