Expression of Cholecystokinin type-A Receptor in Gallbladder with stones

我们发现，胆囊收缩素A型受体（CCKAR）mRNA在大鼠胰腺中的表达随出生后的发育而逐渐增加，而在胎儿胰腺中未见表达。CCKAR基因的表达与胰腺特异性DNA去甲基化有关。用酶切和化学测序法测定去甲基化位点。在该基因的启动子区存在CpG位点。未观察到该基因第2外显子CpG基序的去甲基化与基因表达的明显相关性。在其他组织中，如肝、肾和全脑，DNA残基在胎儿至成人中保持甲基化，并且在这些大鼠组织中未观察到CCKAR表达。在人A型胆囊收缩素受体基因启动子区发现两个碱基的变化，即-128位G → T和-81位A → G。在队列研究的1296例个体中，25例（1.9%）检测到纯合子（T/T，G/G）。与野生型和杂合子相比，多型体脂肪百分比和血清胰岛素和瘦素水平显著升高。

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.