|Budget Amount *help
¥1,600,000 (Direct Cost : ¥1,600,000)
Fiscal Year 1993 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1992 : ¥1,100,000 (Direct Cost : ¥1,100,000)
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.