CYP3A5~＊ 3和MDR1 G2677T/A基因多态性对肾移植患者环孢素A血药浓度及疗效的影响

Effects of CYP3A5~* 3and MDR1 G2677T/AGenetic Polymorphism on Concentration and Efficacy of Cyclosporin in Renal Transplant Patients

目的研究CYP3A5*3和MDR1 G2677T/A基因突变对肾移植术后患者服用环孢素A浓度/剂量×体表面积(C/D')、不良反应和急性排斥反应的影响。方法采用聚合酶链反应(PCR)和限制性内切片段长度多态性(RFLP)方法检测141例肾移植患者CYP3A5*3和MDR1 G2677T/A基因型,比较不同基因型患者之间环孢素A的C/D'值、不良反应和急性排斥反应发生率的差异。结果 CYP3A5*1/*1和CYP3A5*1/*3患者术后7、14、30 d的C0/D'值明显低于CYP3A5*3/*3型患者(P<0.01),组间不良反应和急性排斥反应发生率却无显著性差异(P>0.05);MDR1 2677位点野生型(GG)、突变杂合型(GT﹢GA)、突变纯合型(TT﹢AA﹢AT)3组基因型患者术后7、14、30 d的C0/D'值及7、30 d的C2/D'值存在显著性差异(P<0.05),突变型C/D'值高于野生型,3个月内的急性排斥反应发生率低于野生型(P<0.05),组间不良反应发生率无显著性差异(P>0.05)。结论 CYP3A5*3和MDR1 G2677T/A基因多态性与C/D'值显著相关,且MDR1 G2677T/A与肾移植患者的急性排斥反应存在联系,用药前检测两种基因型有助于环孢素A的个体化给药。

OBJECTIVE To investigate the effects of CYP3A5＊3 and MDR1 G2677T/A on concentration/dosage＊body surface area ratio（C/D′） and adverse effects of cyclosporine and acute rejection in renal transplant patients.METHODS The CYP3A5＊3 and MDR1 G2677T/A genotypes of 141 renal transplant patients treated with cyclosporine were determined by PCR-RFLP method.The differences in C/D′ ratios,adverse reactions and acute rejection were compared among all of the genotype groups.RESULTS The C0/D′ ratios of CYP3A5＊1/＊1 and CYP3A5＊1/＊3 carriers were significantly lower than those of CYP3A5＊3/＊3 patients on 7th,14th and 30th day after renal transplantation,while no significant difference was observed in adverse effects and acute rejection among different genotypes.The C/D′ ratios of three MDR1 G2677T/A genotypes showed significant difference on 7th,14th and 30th day after renal transplantation except C2/D′ ratios on 14th day.The wild-type（G/G） had lower C/D′ ratios than mutant.The acute rejection incidenc showed significant difference among the three groups in three months without significant difference in adverse effects.CONCLUSION CYP3A5＊3 and MDR1 G2677T/A are correlated with C/D′ ratios in renal transplant patients,and the incidence of acute rejection in the three groups of MDR1 G2677T/A genotypes is significantly different.Clinical application of pharmacogenetic studies will be helpful for the individualization of cyclosporine dosage.