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/*3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/*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.

abstractsObjective To investigate the role of polymorphism of cytochrome P450 3A family pol ypeptide 5 (CYP3A5) 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 result.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 dynamic follow-up period,the Tac through concentrations of the individual carried CYP3A5 * 3/* 3 were higherthan 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.