Clinical study for the pathogenesis of idiopathic chronic pancreatitis.

我们研究遗传异常对家族性慢性胰腺炎（CP）的影响，以了解慢性胰腺炎的发病机制。我们查阅了家族性胰腺炎的报告。在日本报道了来自20个家族的74例遗传性慢性胰腺炎患者，其中胰腺炎在两代或两代以上发生在两个以上的血液相关人群中。其中70%的胰腺炎发病年龄小于20岁。46%的病例出现胰腺钙化。3名患者死于胰腺癌。家族性CP没有遗传异常的报道。我们测定了HLA抗原，在14例家族性CP患者中发现DR-2型HLA频率增高。外周血淋巴细胞制备基因组DNA，用EcoRI、HindIII、BamHI、StagI酶切。southern blot分析显示，在两个家族的受影响成员的基因组DNA中，胰腺分泌性胰蛋白酶抑制剂（PSTI）和reg i - β既没有重排，也没有明显缺失。通过聚合酶链反应（PCR）从基因组DNA中扩增出PSTI基因的4个外显子，并对其进行直接测序。家族性CP患者PSTI基因有1个单碱基改变。但是我们还没有证实这个区域影响了蛋白质的合成。家族性CP患者未发现全基因突变。

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.