肝肾移植抗排斥药MMF代谢存在显著个体差异，本课题组既往研究发现单从遗传学不能完全解释其原因。许多研究表明药物相互作用是代谢个体差异的重要因素。我们前期发现Vit D上调UGT1A8/1A10表达，生物信息学提示UGT1A8/1A10基因上游包含Vit D受体VDR的结合位点VDRE，VDRE可启动下游基因表达。鉴于UGT1A8/1A10是MMF重要的代谢酶，我们分析是否存在Vit D→VDR→VDRE→UGT→MMF药物相互作用途径？Vit D能否通过该途径加快MMF代谢，从而与MMF代谢个体差异相关？值得深入研究。为此，本课题将在细胞水平研究Vit D对MMF代谢的影响；在动物实验和临床研究中加以验证；最后在从VDRE入手在分子水平探讨两者相互作用的分子机制。本课题着重从药物相互作用角度阐述MMF代谢个体差异机制，与既往遗传学研究结果相结合，更全面阐明其代谢个体差异机理并指导临床用药。

The MMF metabolism has significant individual difference in the patients after liver and kidney transplantation, the reason of which cannot be completely explained only by genetics data according to previous research findings of our research group. Many research indicated that drug-drug interaction is an important reason. Our earlier studies discovered that 1,25-(OH)2D3 up-regulates the expression of UGT1A8/1A10 which were the important MMF metabolic enzymes.Biological information analysis indicated that up-stream of UGT1A8/1A10 include combining site of Vit D receptor- - Vitamin D responsive element(VDRE),and VDRE can set up the expression of down-stream genes.So we aim to explore wether there is the drug-drug intereaction pathway of Vit D→VDR→VDRE→UGT→MMF. Wether Vit D could accellerate metabolism of MMF agent, and relate to individual difference of MMF metabolism. The question is worth of deeply studying. Therefore, we will study the interference of Vit D on MMF metabolism at molecular level;Verify in the animal model and clincal study;and finally discuss the mechanism of drug-drug interference between Vit D and MMF from the molecular level. Importantly, the proposal is going to elucidate the individuality of MMF metabolism from the view of drug-durg interaction, and more comprehensively explain the reason for individual difference of MMF metabolism in the light of the previous genetic research findings, so as to effective guide clinical medication.