CYP3A5基因多态性对中国肾移植受者他克莫司血药浓度和疗效的影响

Effect of CYP3A5 genetic polymorphism on blood drug concentration and efficacy of tacrolimus in Chinese renal transplant recipients

目的研究CYP3A5基因多态性对肾移植受者他克莫司(FK506)血药浓度/剂量比(blood drug concentration/dose,C/D),术后急性排斥反应(AR)及不良反应发生率的影响。方法采用聚合酶链反应-限制性片段长度多态性技术检测肾移植受者CYP3A5基因型,并以直接测序法进行验证。比较不同基因型患者之间的FK506C/D值,AR、不良反应的发生率。结果肾移植术后3个月内,*3/*3基因型患者FK506的C/D值为149±59,明显高于*1/*1基因型和*1/*3基因型患者的78±24和90±42(均为P<0.05);移植术后3个月内*1/*1基因型患者的AR发生率与*1/*3基因型和*3/*3基因型患者的AR发生率比较差异无统计学意义。与*1/*1基因型和*1/*3基因型患者比较,*3/*3基因型患者术后肝功能异常、药物肾毒性不良反应的发生率较高(均为P<0.05)。结论 CYP3A5基因多态性对服用FK506肾移植患者的C/D值、肝功能异常、药物肾毒性有一定影响。CYP3A5*3/*3基因型患者的FK506的C/D值、肝功能异常和药物肾毒性不良反应的发生率较高。

Objective To investigate the effect of CYP3A5 genetic polymorphism on the blood drug concentration/dose （C/D） ratio, incidence of acute rejection and adverse reaction of tacrolimus （FK506） in Chinese renal transplant recipients. Methods The CYP3A5 genotype of renal transplant recipients was detected by polymerase chain reaction（ PCR）restricted fragment length polymorphism （RFLP） method and compared by direct sequencing. The FKS06 C/D ratio, the incidence of acute rejection and adverse reaction were compared among all of the different genotype groups. Results During the first 3 months after transplantation, the C/D ratio of FKS06 in patients with ＊ 3/＊ 3 genotype was 149 ± 59, which was higher than ＊ 1/＊ 1 geno- type group 78 ±24 and ＊ 1/＊ 3 genotype 90 ±42 （ all in P 〈0.05 ）. Compared with ＊ 1/＊ 3 and ＊ 3/＊ 3 genotypes, there was no significant difference in the incidence of acute rejection of ＊ 1/＊ 1 genotype during the first 3 months after transplantation. Compared with ＊ 1/＊ 1 and ＊ 1/＊ 3 genotypes, the incidence of adverse reaction of liver dysfunction and nephrotoxicity was significantly higher in ＊ 3/＊ 3 genotype （ all in P 〈 0. 05 ）. Conclusions There is definite relation between CYP3A5 genetie polymorphism and FK506 C/D ratio, adverse reaction of liver dysfunction and nephrotoxieity of renal transplant recipients. The FK506 C/D ratio, the incidence of adverse reaction are high in patients of CYP3A5 ＊ 3/＊ 3 genotype.