2001 Fiscal Year Final Research Report Summary
Expression of Cholecystokinin type-A Receptor in Gallbladder with stones
| Project/Area Number |
10670525
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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 | National Children's Medical Research Center |
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Principal Investigator |
KONO Akira National Childrens Medical Research Center, Research Scientist, 研究員 (90161877)
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| Project Period (FY) |
1998 – 1999
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| Keywords | CCKAR / Gene Expression / DNA methylation / DNA polymorphism / Gallstone / Gallbladder / fat deposition |
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| Research Abstract |
We found that mRNA of cholecystokinin type-A receptor (CCKAR) is gradually expressed during postnatal development in rat pancteas, though it is not observed in fetal pancreas. The expression of CCKAR gene correlated to the pancreas-specific DNA demethylation of the gene. The demethylation sites was determined by restriction-enzyme digestion and chemical seaqencing. It was CpG resion in the promoter of the gene. Clear correlation between demethylation of CpG resion in exon 2 of the gene and the gene expression was not observed. In other tissues, such as liver, kidney and whole brain, the DNA resions remained methylated in fetal through adult and CCKAR expression was not observed in those rat tissues. Those results may indicate CCKAR expression is regurated by postnatal development of rat pancreas and that is tissue specific.
We also found two base changes in promoter region of human cholecystokinin type-A receptor gene, a G to T change in -128 nucleotide and an Ato G change in -81 nucleotide. The homozygote (T/T,G/G) was detected in 25 of 1296 individuals(1.9%) in the cohort study. The polymorphysm showed a significantly higher percent body fat and higher levels of serum insulin and leptin, compared with wild type and heterozygotes.
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