Reduced CFTR function and the pathobiology of idiopathic pancreatitis
Reduced CFTR function and the pathobiology of idiopathic pancreatitis
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DOI：
10.1097/01.mcg.0000155522.89005.bf
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发表时间：
2005-04-01
影响因子：
2.9
通讯作者：
Cohn, JA
中科院分区：
文献类型：
--
作者：
Cohn, JA
特发性慢性胰腺炎（ICP）是儿童和非酗酒成人慢性胰腺炎的主要原因。囊性纤维化基因 (CFTR) 和胰蛋白酶抑制剂基因 (PSTI) 突变的个体发生 ICP 的风险增加。在美国和法国的研究中，CFTR 基因有两个异常拷贝时，ICP 风险增加约 40 倍，N34S PSTI 突变增加约 14 倍，两者都有约 500 倍。当ICP患者有两个异常的CFTR基因拷贝时，根据临床发现和鼻腔离子转运反应，也有证据表明胰外组织中残留的CFTR蛋白功能降低。因此，胰管 (CFTR) 和腺泡 (PSTI) 均异常的个体患胰腺炎的风险最高。这些发现表明 PSTI 是 CFTR 相关 ICP 的修饰基因，对胰腺炎的诊断和发病机制具有重要意义。
Idiopathic chronic pancreatitis (ICP) is the leading cause of chronic pancreatitis in children and nonalcoholic adults. The risk of developing ICP is increased in individuals who have mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). In studies from the United States and France, the risk of ICP is increased about 40-fold by having two abnormal copies of the CFTR gene, about 14-fold by having the N34S PSTI mutation, and about 500-fold by having both. When ICP patients have two abnormal copies of the CFTR gene, there is also evidence of reduced residual CFTR protein function in extrapancreatic tissues based on clinical findings and nasal ion transport responses. Thus, pancreatitis risk is highest in individuals who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI). These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the diagnosis and pathogenesis of pancreatitis.