Objective To evaluate the influence of the cytochrome P450（CYP）3A5 genes of both donorsand recipients on the concentration/dosage ratio（C/D） of tacrolimus in adult liver transplant patients. Methods 51adult liver transplant patients received tacrolimus were included in this study. The CYP3A5 polymorphism （includingdonors and recipients） were measured at the time of transplantation，and then tacrolimus-based immunosuppressivetherapy was started on the basis of each patient's genetic constitution. CYP3A5 * 1/ * 1 genotype and  * 1/ * 3 genotypewere combined into expressor genotype and * 3/ * 3 genotype was nonexpressor group. The C/D of tacrolimus during3 months after surgery was analyzed in relation to the CYP3A5 genotype. A stepwise regression was used to analyze the relationship between C/D of tacrolimus and genotype，time course，age，liver weight in liver transplantpatients.Results C/D of tacrolimus in patients with CYP3A5 * 1 expressed donor was lower than C/D of patientswith CYP3A5 * 1 unexpressed donor（P＜0.05 or P＜0.01）； C/D in CYP3A5 * 1-carried patients was also lowerthan CYP3A5 * 1 unexpressed patients（all P＜0.01）. C/D in CYP3A5 * 3/ * 3 patients with CYP3A5 * 3/ * 3 donorwas obviously higher campared with the other 3 groups during 3 months after transplantation（all P＜0.01），andthe difference of C/D in other 3 groups was not statistically significant （all P＞0.05）.The regression equation：Y（tacrolimus concentration/dose ratio per unit weight） ＝ 1.025 + 0.625 donor genotype + 0.520 receptor genotype +0.021 postoperative length － 0.008 patients with age. Conclusions Those findings suggest that the CYP3A5 * 1genotype in donors as well as in patients both contributes to inter-individual variation in the C/D of tacrolimus in adultliver transplantation.The factors impacting patient's tacrolimus blood concentrations are donor's CYP3A5 genotype， recipient's CYP3A5 genotype，time course and age . Patients can benefit from setting and adjusting FK506 dosageaccording to CYP3A5 genotype of both donors and recipients.

Liver transplantation, Tacrolimus, Cytochrome P4503A5, Pharmacogenomics

目的 探讨成人肝移植供体和受体细胞色素 P450（CYP）3A5 酶 6986 位点的基因多态性对肝移植术后普乐可复（他克莫司，FK506）浓度 / 剂量比的影响。方法 选择 2010 年 11 月到 2011 年 11 月本中心共 51 例肝移植患者。术前收集肝移植受体和供体血，进行 CYP3A5 基因分型检测，根据供受体基因型分别分组，CYP3A5*1/*1 及 CYP3A5*1/*3 均为 CYP3A5 表达型，属于快代谢组，CYP3A5*3/*3 为 CYP3A5非表达型，属于慢代谢组。记录患者术后 2 个月内每周及术后第 3 个月他克莫司剂量、血药浓度，比较不同基因型供、受体之间他克莫司的浓度 / 剂量比，探求它和基因型之间的关系。并通过回归分析探索非基因型因素对他克莫司浓度 / 剂量比的影响。结果 根据供体基因型分组，供体快代谢组较慢代谢组术后1 周至 3 个月浓度 / 剂量比显著降低（P＜0.05 或 P＜0.01）；根据受体基因型分组，受体快代谢组较慢代谢组术后 3 周至 3 个月浓度 / 剂量比有显著差异（均 P＜0.01）；供 / 受体均为 CYP3A5*3*3 组和其他 3 组比较，浓度 / 剂量比有显著差异（均 P＜0.01），供 / 受体表达组、供体表达 / 受体无表达组和受体表达 / 供体无表达组 3 组的浓度 / 剂量比逐渐升高，但是差异无统计学意义（P＞0.05）。回归方程为 ：Y（他克莫司血药浓度 / 单位体重剂量比）＝1.025+0.625 供体基因型 + 0.520 受体基因型 + 0.021 术后时长－ 0.008 患者年龄。结论 供、受体的 CYP3A5 基因多态性都是影响肝移植术后患者他克莫司血药浓度的重要因素，供、受体都是慢代谢型的患者血药浓度 / 剂量比会更高。术后早期影响他克莫司浓度 / 剂量比的因素依次为 ：供体基因型、受体基因型、术后时长、患者年龄。根据代谢类型调整 FK506 剂量，对于供体、受体双慢代谢的患者临床上慎重增加剂量，用药前检测基因型可以更有效地对他克莫司进行剂量调整。

肝移植 , 他克莫司 , 细胞色素 P450 3A5 酶 , 基因多态性