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

 【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。

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

【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(C0) 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.