他克莫司用于骨髓移植后免疫抑制治疗，其疗效在不同患者间差异明显。CYP3A5是他克莫司主要代谢酶，CYP450氧化还原酶（POR）影响CYP450代谢过程。我们前期研究结果提示POR*28基因多态性影响健康人群他克莫司体内代谢。为此，我们提出假说：POR*28可能通过影响CYP3A5酶活性，影响骨髓移植患者他克莫司代谢。为了验证这一假说，我们以骨髓移植患者为研究对象探索POR*28基因多态性对CYP3A5酶活性及对他克莫司代谢的影响，在此基础上通过白血病肿瘤细胞，体外酶反应体系多方面多层次验证这一影响并探索作用机制。本研究将明确POR*28基因多态性对骨髓移植患者他克莫司体内代谢的影响，初步描绘他克莫司代谢影响模式，为他克莫司个体合理给药提供指导。

Tacrolimus has been used in immunosuppressive therapy after bone marrow transplantation and its clinical effect differs significantly among patients. CYP3A5 is a major metabolic enzyme of tacrolimus and its metabolic processes can be affected by CYP450 reductase (POR). Our previous study suggests that POR*28 genetic polymorphism affects tacrolimus pharmacokinetics in chinese healthy population. On this basis, we propose the hypothesis that POR*28 may influence the tacrolimus metabolism in bone marrow transplantation recipients through regulating CYP3A5 activity. To verify this hypothesis, we will explore the relationship of POR*28 genetic polymorphism with CYP3A5 activity and tacrolimus metabolism in bone marrow transplantation patients. Furthermore, we will validate the effect and explore the underlying mechanism in human promyelocytic leukemia cells and enzyme reaction system in vitro. This study will identify the effect of POR*28 genetic polymorphism on tacrolimus metabolism in bone marrow transplantation patients in vivo, depict the metabolic characteristics of tacrolimus and provide guidance for rational personalized medicine of tacrolimus.