供受体CYP3A5和MDR1基因多态性与肝移植术后患者他克莫司浓度/剂量比的关系  

Effect of CYP3A5 and MDR1 Gene Polymorphism in both Donor and Recipient on Concentration/Dose Ratios of Tacrolimus in Liver Transplant Patients

作　　者：李洋[1] 姜楠[1] 郭宇[1] 陈冠中[1] 张琪[1] 陆敏强[1] 杨扬[1] 陈规划[1] 

机构地区：[1]中山大学附属第三医院肝移植科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2012年第1期49-53,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家重点基础研究发展计划(973计划)(2009CB522404);广州市科技计划项目(2009Z1-E211)

摘　　要：【目的】研究肝移植供受体CYP3A5和MDR1基因多态性对患者术后他克莫司浓度/剂量比的影响。【方法】选取我中心32例肝移植供受体,测定患者术后1、2、4、12周体质量、他克莫司用量及药谷浓度等指标,采用聚合酶链式反应-限制性内切片段长度多态性(PCR-RFLP)方法测定供受体基因分型,比较不同基因型对患者他克莫司浓度/剂量比值的影响。【结果】供体CYP3A5*1/*1和*1/*3型患者术后2、4、12周他克莫司浓度/剂量比明显低于*3/*3型患者(P<0.05);受体CYP3A5*1、*3基因型,供受体MDR1 2677GG、GA基因型各组间他克莫司浓度/剂量比差异无统计学意义(P>0.05)。联合分析供受体CYP3A5基因型,术后2、4、12周,不论受体基因型如何,供体为CYP3A5*3/*3基因型患者他克莫司浓度/剂量比均高于供体为CYP3A5*1/*1和CYP3A5*1/*3基因型患者(P<0.05);供体基因型相同时,受体组间差异无统计学意义(P>0.05)。【结论】肝移植供体CYP3A5*3基因多态性与他克莫司浓度/剂量比明显相关,供体携带*1等位基因的患者需更高剂量他克莫司才能达到目标血药浓度。[Objective] To investigate the effect of CYP3A5 and MDR1 polymorphism in the donor/recipient on the concentration /dose ratio of Tacrolimus in Chinese liver transplant patients. [ Methods] Blood samples were collected from liver transplant patients who received Tacrolimus in the third affiliated hospital of Sun Yat-sen university, and the tissue samples were collected from the corresponding donors. The CYP3A5 andMDR1 genotypes were determined by PCR-RFLP method. At 1,2,4 and 12 weeks after transplantation, Tacrolimus doses （mg/kg/day） and trough blood levels （CO） were determined. [Results] The concentration /dose ratios of patients with CYP3A5 ＊ 1 / ＊ 1 and CYP3A5 ＊ 1/＊ 3 donors were significantly lower than those with CYP3A5 ＊ 3/＊ 3 patients at 2,4 and 12 weeks after liver transplantation. No difference was found among the MDR1 genotypes in donor/recipients or CYP3A5 genotypes in recipients. The same results were found in the analysis of the combination of both dornors and recipients. [Conclusion] CYP3A5 ＊ 1/＊ 3 polymorphism in the donor is correlated with the whole blood concentration/dose ratio in Chinese liver transplant patients. Donors with CYP3A5 ＊ 1 allele require more tacrolimus to reach target concentrations compared to those with CYP3A5 ＊ 3/＊ 3 genotype.

关 键 词：肝移植 他克莫司 CYP3A5 MDR1 基因多态性 

分 类 号：R737.25[医药卫生—肿瘤]