Study for the molecular pathogenesis of the idiopathic chronic pancreatitis, especially familial pancreatitis
| Project/Area Number |
08670547
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
KOIZUMI Masaru Tohoku Univ.School of Medicine, Lecturer, 医学部, 講師 (40111281)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOSEGAWA Tooru Tohoku Univ.School of Medicine, Associate Professor, 医学部・附属病院, 助教授 (90226275)
SATO Kenichi Tohoku Univ.School of Medicine, Research Associate, 医学部・附属病院, 助手 (10282055)
NATA Kouji Tohoku Univ.School of Medicine, Research Associate, 医学部, 助手 (90202233)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Chronic pancreatitis / Hereditary pancreatitis / Trypsinogen gene mutation / familial pancreatitis |
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| Research Abstract |
We studied genetic abnormalities affecting familial chronic pancreatitis (CP) in order to understandg its pathogenesis. We reviewed the reports of familial pancreatitis in Japan and the world. Hereditary pancreatitis was diagnosed according to Gross's criteria, that is, the family included more than two pancreatitis patients in two generations and their onset was before the age of ten. However, it was difficult to employ Gross's criteria in Japan because of the decrease in the size of families.
We did not find the genetic abnormalities in familial CP using southern blot analysis of pancreatic secretary trypsin inhibitor (PSTI) gene, Reg I-alpha gene and Reg I-beta gene. Recently, two mutations, R117H and N21I,in cationic trypsinogen gene were reported in American and Italian families (Whitcomb, 1996 and 1997). The R117H mutation induces the disappearance of active trypsin at acute inflammation.
We extracted genomic DNA from twenty-four outpatients in our clinic who showed symptoms of pancreatitis in childhood and four healthy relatives in 17 families. The R117H mutation in exon 3 was found in the seven patients with acute pancreatitis in four families. All of them presented the symptoms before 28 years old and had pancreatic calcification. But the N21I mutation in exon 2 was detected in no families. And we did not find other changes in the trypsinogen gene. We could diagnose the hereditary pancreatitis through the trypsiongen gene mutation in only one pancreatitis patient regardless of the age of onset and number of patients in the family. This study revealed that the trypsinogen gene mutation in exon 3 was common and an important factor in Japanese hereditary pancreatitis, as in Caucasians. Conclusively, the trypsin plays a major role in the pathogenesis of pancreatitis.
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Report
(3 results)
Research Products
(14 results)
