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Expression of Cholecystokinin type-A Receptor in Gallbladder with stones

胆囊收缩素A型受体在胆囊结石中的表达

基本信息

批准号：
10670525
负责人：
KONO Akira
金额：
$ 1.15万
依托单位：
National Children's Medical Research Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670525/
关键词：
CCKAR Gene Expression DNA methylation DNA polymorphism Gallstone Gallbladder fat deposition 発現制御胆嚢 DNA脱メチル化膵臓

项目摘要

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.

我们发现胆囊收缩素A型受体（CCKAR）的mRNA在大鼠胰腺的出生后发育过程中逐渐表达，但在胎儿胰腺中没有观察到。 CCKAR基因的表达与该基因的胰腺特异性DNA去甲基化相关。通过限制性酶消化和化学测序确定去甲基化位点。这是基因启动子中的 CpG 片段。未观察到基因外显子 2 中 CpG 区域的去甲基化与基因表达之间存在明显的相关性。在其他组织中，如肝脏、肾脏和全脑，DNA 片段在胎儿至成年期间仍保持甲基化，并且在这些大鼠组织中未观察到 CCKAR 表达。这些结果可能表明CCKAR的表达受到大鼠胰腺出生后发育的调节，并且具有组织特异性。我们还发现人胆囊收缩素A型受体基因启动子区有两个碱基变化，-128个核苷酸的G到T的变化和-81个核苷酸的Ato G的变化。队列研究中1296人中有25人（1.9%）检测到纯合子（T/T、G/G）。与野生型和杂合子相比，多态性显示出显着更高的体脂百分比以及更高水平的血清胰岛素和瘦素。