基于孕烷X受体基因多态性指导肾移植受者他克莫司的个体化用药

摘要

目的:研究肾移植受者孕烷X受体(PXR-C24381A)基因多态性与他克莫司(FK506)给药剂量的关系.方法:采用聚合酶链反应(PCR)产物直接测序法对60例肾移植术后受者进行PXR-C24381A基因分型,采用酶联免疫吸附分析法(ELISA法)测定FK506的血药浓度,比较不同基因型患者FK506血药浓度与给药剂量比值(C/D值)的差异.结果:肾移植受者PXR-C24381A等位基因C的频率为75％,A的频率为25％.C/A基因型与C/C基因型患者C/D值显著高于A/A基因型患者(P＜0.05).结论:肾移植受者PXR-C24381A基因多态性与FK506血药浓度具有相关性,A/A基因型患者拟取得相似的血药浓度需要比C/A和C/C基因型患者服用更高剂量的FK506.%OBJECTIVE:To study the relationship between pregnane X receptor (PXR-C24381A) genetic polymorphism and dosage of tacrolimus (FK506) in kidney-transplanted patients.METHODS:The PXR genotypes of 60 kidney-transplanted patients were determined by PCR-direct sequencing.Blood concentration of FK506 was measured by ELISA.The blood concentration of FK506 in patients with different genotypes was compared with dosage (C/D ratio).RESULTS:The frequency of PXR-C24381A allele C was 75％,and that of allele A was 25％.C/D ratio of patients with A/A genotype was significantly lower than those with C/A genotype or C/C genotype (P＜0.05).CONCLUSIONS:PXR-C24381A polymorphism is correlated with the blood concentration of FK506 in kidney-transplanted patients.If the same blood concentration of FK506 is presented in three genotypes,patients with A/A genotype should take higher dosage than those with C/C and C/A genotypes.