Clinical study for the pathogenesis of idiopathic chronic pancreatitis.

为了解家族性慢性胰腺炎（CP）的发病机制，我们对CP的遗传异常进行了研究。本文复习了家族性胰腺炎的文献报道。在日本报告了来自20个家族的74例遗传性慢性胰腺炎患者，其中胰腺炎发生在两代及两代以上的两个以上血亲中。其中70%的人胰腺炎发病年龄不到二十岁。46%的病例中观察到胰腺钙化。3例患者死于胰腺癌，无家族性CP遗传异常的报道。本文对14例家族性CP患者进行了HLA抗原检测，发现HLA DR-2型频率增高，用EcoRI、HindIII、BamHI、StagI酶切外周血淋巴细胞基因组DNA，Southem印迹分析显示两个家族的患者基因组DNA中既无PSTI和reg I-β的重排，也无PSTI和reg I-β的缺失。采用聚合酶链反应（PCR）技术从基因组DNA中扩增PSTI基因的4个外显子，并直接测序。家族性CP患者PSTI基因有一个碱基改变。但我们还没有证实该区域影响蛋白质的合成。未发现家族性CP患者reg I β基因的突变。

We studied the genetic abnormality affected the familial chronic pancreatitis (CP) for understanding the pathogenesis of chronic pancreatitis. Wereviewed the reports of familial pancreatitis. Seventy-four hereditary chronic pancreatitis patients from twenty families, in whom pancreatitis occurred in more than two blood-related persons in two and more generations, were reported in Japan. In 70% of them, the onset of pancreatitis is less than twenty years old. Pancreatic calcifications were observed in 46% of cases. Three patients died of pancreatic cancer.No genetic abnormality in the familial CP has been reported. We determined the HLA antigen and increased frequency of the HLA types DR-2 was seen in fourteen familial CP patients in our clinic.Genomic DNA was prepared from peripheral lymphocytes and digested with EcoRI,HindIII,BamHI,StagI.Southem blot analysis revealed neither a rearrangement nor a gross deletion of pancreatic secretory trypsin inhibitor (PSTI) and reg I-beta in genomic DNA of affected members of two families. Four exons of PSTI gene amplified by polymerase chain reaction (PCR) from genomic DNA was directly sequenced. One single-base change in the PSTI gene of familial CP patient was observed. But we hava not confirmed this region influenced the synthesis of protein. And we could not find the mutation of whole reg I-beta gene of familial CP patients.