Mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene in Japanese patients with pancreatitis
Mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene in Japanese patients with pancreatitis
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DOI：
10.1159/000086535
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发表时间：
2005-01-01
期刊：
影响因子：
3.6
通讯作者：
Shimosegawa, T
中科院分区：
文献类型：
--
作者：
Kume, K;Masamune, A;Shimosegawa, T
背景/目的：最近的研究表明丝氨酸蛋白酶抑制因子1(SPINK1)基因的N34S突变与慢性胰腺炎(CP)有关。我们在这里研究了日本胰腺炎患者中SPINK1突变的流行率。方法：提取80例日本CP患者、36例急性胰腺炎(AP)患者和165例健康对照的基因组DNA。用聚合酶链式反应扩增SPINK1基因的所有外显子和启动子区域，并直接测序。结果：发现4种突变类型(N34S、IVS1-37T>；C、-215G>；A和IVS3+2T>；C)和两种多态类型(-253T>；C和272C>；T)。N34S突变与IVS1-37T和GT；C共分离，8例CP和1例AP患者存在N34S突变。-15G>；A突变与IVS3+2T>；C完全连锁，8例CP和1例AP患者存在-15G>；A突变。家族性胰腺炎组和特发性胰腺炎组[N34S；IVS1-37T>；C]和[-215G>；A；IVS3+2T>；C]频率分别为38%和13%，显著高于正常对照组(0.6%和0%)。此外，自身免疫性CP患者的[N34S；IVS1-37T>；C]突变频率较高(33%)。结论：在日本，SPINK1基因突变也与胰腺炎有关。版权所有(C)2005 S.Karger AG，巴塞尔和IAP。
Background/Aims: Recent studies have shown an association between the N34S mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene and chronic pancreatitis (CP). We here examined the prevalence of SPINK1 mutations in Japanese patients with pancreatitis. Methods: Genomic DNA was prepared from 80 Japanese patients with CP, 36 patients with acute pancreatitis (AP), and 165 healthy controls. All exons and the promotor region of the SPINK1 gene were amplified by the polymerase chain reaction, and directly sequenced. Results: We found four types of mutation (N34S, IVS1-37T>C, -215G>A, and IVS3 + 2T>C) and two types of polymorphism (-253T>C and 272C>T). The N34S mutation cosegregated with IVS1-37T>C, and was present in 8 CP and 1 AP patients. The -15G>A mutation was in a complete linkage with IVS3 + 2T>C, and was present in 8 CP and 1 AP patients. The prevalences of [N34S; IVS1-37T >C] and [-215G>A; IVS3 + 2T>C] were significantly higher in patients with familial pancreatitis (38 and 13%, respectively) and with idiopathic CP (13 and 16%) than normal subjects (0.6 and 0%). In addition, the frequency of [N34S; IVS1-37T>C] mutation was higher in patients with autoimmune CP (33%). Conclusion: The SPINK1 gene mutations were associated with pancreatitis also in Japan. Copyright (C) 2005 S. Karger AG, Basel and IAP.