基因多态性与肾移植患者他克莫司个体化治疗研究进展

目的:他克莫司(tacrolimus,FK506)是防治肾移植术后排斥反应的常用药,其狭窄的治疗窗和药动学及药效学方面显著的个体差异一直困扰着临床。现有研究表明,CYP3A4、CYP3A5、MDR1单倍型以及IL-10、PXR基因多态性可能对FK506的药动学和药效学产生不同影响,进一步深入研究基因多态性对临床实施肾移植患者个体化治疗具有十分重要的意义。方法:对国内外近期文献进行分析。结果与结论:进一步系统查明CYP3A4、CYP3A5、MDR1单倍型以及IL-10、PXR基因多态性对指导肾移植患者FK506个体化用药具有十分重要的意义。

Research Progress on Genetic Polymorphisms and Individualized Therapy of Tacrolimus in Renal Transplant Recipients

OBJECTIVE: Tacrolimus(FK506) is the commonly used drug against rejection reaction following renal transplantation,but its narrow therapeutic window and individual differences in pharmacokinetics and pharmacodynamics has been a problem in clinical practice.Research have indicated that the haplotype of CYP3A4,CYP3A5,multi-drug resistance gene 1(MDR1),and the polymorphisms of interleukin-10(IL-10) and pregnane X receptor(PXR) might have different influence on the pharmacokinetics and pharmacodynamics of FK506.Further study on the association of gene polymorphisms with individualized tacrolimus therapy of renal transplant recipients is of great significance in the clinical setting.METHODS: The pertinent medical literature in recent years both at home and abroad was reviewed.RESULTS & CONCLUSION: Further systematic review of literature revealed the great significance of the haplotype of cytochrome CYP3A4,CYP3A5 and multi-drug resistance gene 1(MDR1) and the polymorphisms of interleukin-10(IL-10) and pregnane X receptor(PXR) as guidance for the individualized therapy of FK506 in renal transplant recipients.