Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis
Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis
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DOI：
10.1007/s100380170082
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发表时间：
2001-01-01
影响因子：
3.5
通讯作者：
Horii, A
中科院分区：
文献类型：
--
作者：
Kaneko, K;Nagasaki, Y;Horii, A
慢性胰腺炎（CP）是一种持续性或复发性胰腺炎性疾病。几项研究表明，阳离子胰蛋白酶原（PRSS 1）基因和囊性纤维化跨膜传导调节因子（CFTR）基因的突变是遗传性和/或特发性CP病例的发病机制的原因。近年来，胰腺分泌型胰蛋白酶抑制剂（PSTI）基因的N34 S改变被认为与遗传性和/或特发性CP的发病机制密切相关。在此，我们分析了32例无亲缘关系的日本CP患者的PSTI基因的遗传改变，这些患者发展为青少年发病的CP或有CP家族史，5例患者被发现在该基因中存在改变。在这5例患者中的3例中，发现了杂合子N34 S改变;该频率显著低于先前报道的高加索患者。此外，在2例患者中，在PSTI启动子区翻译起始位点上游215 bp处观察到一个新的纯合G → A转换（-215 G>A）。我们进一步调查了117名正常人的-215G>A改变;这些人都没有携带这种改变。我们的结果表明，-215G>A的改变，以及N34 S的改变。是CP的诱发因素。
Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. Several studies have demonstrated that mutations in the cationic trypsinogen (PRSS1) gene and the cystic fibrosis transmembrane conductance regulator (CFTR) gene are causative of the pathogenesis in a subset of hereditary and/or idiopathic CP cases. Recently, the N34S alteration of the pancreatic secretory trypsin inhibitor (PSTI) gene has been suggested to be closely associated with the pathogenesis of hereditary and/or idiopathic CP. Herein we analyzed genetic alterations of the PSTI gene in 32 unrelated Japanese CP patients who developed juvenile-onset CP or had a family history of CP, 5 patients were found to harbor alterations in this gene. In 3 of these 5 patients, heterozygous N34S alterations were found; this frequency is significantly lower than that in Caucasian patients reported previously. Moreover, a novel homozygous G-to-A transition in the promoter region of PSTI at 215bp upstream from the translation initiation site (--215G>A) was observed in 2 patients. We further surveyed the -215G>A alteration in 117 normal individuals; none of these individuals harbored this alteration. Our results suggested that the -215G>A alteration, as well as the N34S alteration. is a predisposing factor for CP.