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在大鼠胰腺出生后发育过程中逐渐表达，但在胎儿胰腺中未观察到。CCKAR基因的表达与胰腺特异性DNA去甲基化相关。通过限制性酶切和化学测序确定去甲基化位点。这是基因启动子的CpG变异。该基因外显子2 CpG的去甲基化与基因表达没有明显的相关性。在其他组织中，如肝、肾和全脑，DNA的甲基化在胎儿到成年期间仍然存在，CCKAR在这些大鼠组织中未见表达。这些结果可能表明CCKAR的表达受大鼠胰腺出生后发育的调控，并且具有组织特异性。我们还发现了人胆囊收缩素a型受体基因启动子区域的两个碱基变化，即-128核苷酸的G到T变化和-81核苷酸的Ato G变化。在队列研究中，1296例个体中检测到25例纯合子（T/T,G/G）（1.9%）。与野生型和杂合子相比，多聚体的体脂率、血清胰岛素和瘦素水平显著提高。

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.