Clinical study for the pathogenesis of idiopathic chronic pancreatitis -- Analysis on the pathogenesis of familial chronic pancreatitis using the molecular biological methods

为了探讨慢性胰腺炎（CP）的发病机制，我们确定了什么样的遗传异常影响家族性CP，并回顾了年轻胰腺炎患者和一个家族中胰腺疾病病例的报道。日本报告了来自38个家庭的105名患者，有2例或2例以上的CP病例。遗传CP患者56例，来自15个家族，2代或2代以上有2个以上血缘关系的人发生胰腺炎。家族性CP占日本所有CP病例的0.7% ~ 1.5%。我们门诊共有来自3个家庭的14名患者。在一个有6例CP患者的家族中，我们发现了两例新发男性患者（29岁和24岁，两例患者的儿子），经胰腺钙化和胰管不规则扩张证实。家族性CP没有遗传异常的报道。兄弟CP病例的HLA抗原分析显示，A、B、C和DR位点共发，即均具有A24、BW52、BW54、CW1、DR2和DR4。1 / 4的亲本子代与亲本存在相同的C-位点和dr -位点（CW1, CW3, DR4, DRW9）。本诊所家族性CP患者HLA DR-2型的发生率增高。HLA与胰腺炎的病因关系不明显，认为防御机制在胰腺炎发生中起主要作用。外周白细胞制备基因组DNA，用EcoRI消化。HindIII, BamHI， *和StagI。Southern blot分析显示，两个家族的受影响成员的胰腺分泌胰蛋白酶抑制剂（PSTI）和Reg基因组DNA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的PSTI基因有一个单碱基改变。但是我们还没有证实这个区域影响了蛋白质的合成。

To investigate the pathogenesis of chronic pancreatitis(CP), we determined what kind of genetic abnormality affected the familial CP.We reviewed the reports of young pancreatitis patients and cases of pancreatic disorders in a family. One hundred five patients from 38 families with two and more than two cases of CP have been reported in Japan. There were 56 hereditary CP patients from 15 families, in whom pancreatitis occurred in more than two blood-related persons in over 2 or more generations. Familial CP accounted for 0.7%-1.5% of all cases of CP in Japan. There were 14 patients from 3 families in our clinic. In a kindred having 6 CP patients, we found newly two male patients (29 and 24 years old, two patient's sons) proved by pancreatic calcification and irregular dilatation of the pancreatic duct.No genetic abnormality in the familial CP has been reported. Analysis on the HLA antigens of cases of brothers with CP showed the co-incidence in locus A, B, C, and DR, i.e., both of them possessing A24, BW52, BW54, CW1, DR2 and DR4. One out of four pairs os child and parent in one kindred revealed the same C- and DR-locus(CW1, CW3, DR4, DRW9). Familial CP in our clinic has an increased frequency of the HLA types DR-2. There is no strong relationship between HLA and etiological factors of CP.We think the defensive mechanism plays the mafor role of developing pancreatitis. Genomic DNA was prepared from peripheral leukocytes and digested with EcoRI.HindIII, BamHI, *and StagI.Southern blot analysis revealed neither a rearrangement nor a gross delection of pancreatic secretory trypsin inhibitor(PSTI) and Reg 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 was observed. But we have not confirmed this region influenced the synthesis of protein.