肾移植受者CYP3A5基因多态性对他可莫司代谢的影响

目的研究CYP3A基因多态性对肾移植受者他可莫司代谢的影响。方法50例肾移植受者采用FK506＋霉酚酸酯＋强的松三联免疫抑制方案，FK506起始剂量0．15mg／（kg·d），1w后根据目标血药浓度调整。CYP3A5基因多态性检测采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法，50例肾移植受者分为＊1／＊1型（12例）、＊1／＊3型（16例）、＊3／＊3型（22例）共3组。比较6个月内FK506的血药浓度／剂量比。结果 肾移植术后7天、1月、3月、6月＊3／＊3型患者FK506的血药浓度／剂量比显著高于＊1／＊1型和＊1／＊3型（P〈0．05）。结论由于CYP3A5基因多态性影响，＊1／＊1型组的患者早期难以达到有效FK506目标血药浓度，应该提高该组患者的起始用药剂量，根据CYP3A5基因多态性作为FK506个体化用药的依据，可以减少早期急性排斥反应，提高肾移植的临床效果。

Influence of CYP3A5 genetic polymorphism on tacrolimus metabolism in renal transplant recipients

Objective To study the influence of CYP3A5 genetic polymorphism on tacrolimus metabolism in renal transplant recipients.Methods Fifty patients transplanted with planted cadaver kidney receiving the triple immunosuppressive (taorolimus+mycophenolate mofetil+prednison) were grouped according to CYP3A5 genotype (.1/.1,.1/.3,*3/*3).The initial dose of tacrolimus was 0.15 mg/(kg·d)and the dosage was adjusted according to the blood concentration to a target therapeutic window.Polymerase chain reaction restrict fragment length polymorphism (PCR-RFLP) was performed to genotype CYP3A5.Results Concen-tration-to-dose ratio (CO/D,whereby CO is trough level and D is daily dose per weight) could be calculated on 7th day and on 1,3 and 6 month.The CYP3A5 *3/*3 group had the largest CO/ D and the CYP3A5 *1/*1 group had the smallest CO/D.The statistical significant difference (P<0.05) was found among the three groups.Conclusion This study demonstrates that genetic polymorphism of CYP3A5 are associated with the initial tacrolimus requirments in renal transplant recipients.Patients with the CYP3A5 *1/*1 genotype may need to be given a higher dose of tacrolimus to reach target blood concentration compared with those with the CYP3A5 *3/*3 genotype.Genotyping prior to transplantation may help to assess the initial daily dose required by individual patients for adequate immunosupression.