细胞色素P4503A亚家族多肽5基因多态性对肾移植患者术后他克莫司血药浓度的影响  

Influence of cytochrome P450 3A family polypeptide 5 genetic polymorphisms on tacrolimus in renal transplant patients

作　　者：孙阳洋[1] 魏雪栋[1] 郑浩[1] 张辉[1] 张江磊[1] 侯建全[1] 何军 邱桥成 袁晓妮 

机构地区：[1]苏州大学附属第一医院泌尿外科,215006 [2]江苏省血液研究所

出　　处：《中华实验外科杂志》2013年第4期848-851,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81273266、30872530）;江苏省医学重点学科资助项目（XK201151）;江苏省医学创新团队与领军人才资助项目（LJ201138）;苏州市科技基础设施建设计划项目（SZS201001、SZS0702）

摘　　要：目的探讨不同细胞色素P4503A亚家族多肽5（CYP3A5）基因型与肾移植患者术后钙调磷酸酶抑制剂（CNI）他克莫司（Tac）的药物剂量和患者血清药物谷浓度之间的关系。方法对接受过肾移植的77例患者采用基因测序方法进行CYP3A5基因多态性检测，同时采用微粒酶联免疫法动态检测移植后7、14、21d．1、3、6、12个月Tac的血清药物谷浓度。按CYP3A5的不同基因型，比较各时间段组内不同CYP3A5基因型与血清药物谷浓度、用药剂量之间的相关性。结果77例肾移植患者中，CYP3A5＊1／＊1型8例（10．39%）、CYP3A5＊1／＊3型31例（40．26＊）、CYP3A5＊3／＊3型38例（49．35＊）。肾移植术后1个月内＋3／＊3型患者服用Tac的的血清药物谷浓度高于＊1／＊3型和＊1／＊1型（P〈0．05），而＊3／＊3型患者Tac的用药剂量则低于＊1／：it3型和＊1／＊1型（P〈0．05）；肾移植术后＊3／＊3型患者在3、6、12个月时的血药浓度高于＊1／女3型和＊1／＊1型患者，差异有统计学意义（P〈0．05）。结论CYP3A5＊3／{3型患者在肾移植术后1年内使用较低剂量的Tac即可维持有效的血药浓度。Objective To investigate the role of polymorphism of cytochrome P450 3A family pol- ypeptide 5 （CYP3AS） in determination of tacrolimus metabolism in renal transplant recipients. Methods A total of 77 kidney transplant patients were enrolled in this study. A sequence based typing （SBT） was used for detecting the CYP3A5 genotype. Patients were assigned three genotypes according to the CYP3A5 allele analysis resuh. The trough concentrations of Tac were detected by microparticle enzyme immunoassay respectively. Results At 1 month after transplantation the Tac through concentrations of individuals carried CYP3A5 ＊ 3/＊ 3 were significant higher than those of CYP3A5 ＊ 1 allele （P 〈 0.05 ）. And the dosage of individual carried CYP3A5 ＊ 3/＊ 3 was lower than those of CYP3A5 ＊ 1 allele （ P 〈 0. 05 ） ; In the dynam- ic follow-up period,the Tac through concentrations of the individual carried CYP3A5 ＊ 3/＊ 3 were higher than those of CYP3A5 ＊ 1 allele （ P 〈 0. 05 ）. The Frequency of CYP3A5 genotypes was as follow,8 patients （ 10. 39% ） carried CYP3A5 ＊ 1/＊ 1 genotype,31 patients （40. 26% ） carried CYP3A5 ＊ 1/＊ 3 genotype and 38 patients （49. 35% ） carried CYP3A5 ＊ 3/＊ 3 genotype. Conclusion Compared with the patients carried CYP3A5 ＊ 1 allele,the patients carried CYP3A5 ＊ 3/＊ 3 need less dosage to maintain appropriate concentration in the first year after renal transplantation.

关 键 词：细胞色素P4503A亚家族多肽5 基因多态性 他克莫司 肾移植 

分 类 号：R699[医药卫生—泌尿科学]