MDR1基因多态性对肾移植受者个体化应用他克莫司及预后的影响

Impact of multidrug resistance 1 gene polymorphisms on Tacrolimus regimen and outcome of grafts in renal transplantation recipients

目的研究肾移植受者的多药耐药基因1（MDRI）C3435T和G2677T／A单核苷酸多态性（SNP）对他克莫司（Tac）个体化应用及受者预后的影响。方法对127例移植肾功能稳定的肾移植受者进行随访，采用引物特异性聚合酶链反应技术分析其MDR1基因C3435T和G2677T／A的SNP，并监测受者全血Tac浓度谷值。结果91例（71．65％）接受常规Tac三联免疫抑制治疗（非辅助治疗者），另36例受者（28．35％）需要辅助药物提高Tac浓度（辅助治疗者）。3435C基因型者在辅助治疗者中占68．05％，在非辅助治疗者中占48．35％（P〈0．01）。非辅助治疗者中，MDR1G2677T／A、C3435T各基因型的血Tac浓度／剂量[单位为（μg／L）／（mg／kg）]的差异均无统计学意义（P〉0．05），C3435T-G2677T／A的单倍体分析也为相同结果（P〉0．05）。4年随访期间，13例移植肾功能丧失，其中84．6％（11／13）的受者有MDR13435C基因位点，与移植肾功能正常者相比较，此基因型频率的差异无统计学意义（P〉0．05）。结论对于需要用辅助治疗升高Tac浓度的肾移植受者，其3435C基因型出现的几率高，C基因型受者可能倾向于发生移植肾功能丧失。

Objective To investigate the effect of the polymorphisms of multidrug resistance 1 （MDR1） C3435T and G2677T on Tacrolimus （Tac） individualized treatment and prognosis of grafts in the renal transplantation recipients （RTRs）. Methods One hundred and twenty-seven RTRs who treated with Tac regimen and had a stable graft function were enrolled, and were divided into adjuvant treatment group and non-adjuvant treatment group according to whether given adjuvant drugs to raise Tac trough concentrations. MDR1 C3435T and G2677T SNPs were detected by using sequence specific primers PCR. Tac trough concentrations of whole blood were measured by using enzyme- labeled immunosorbent assay. Tac concentration-to-dose ratio （C/D） standardized by body weight was compared according to the various genotypes and haplotypes of MDR1 C3435T and G2677TA SNPs. Results Adjuvant treatment group including 36 recipients had a higher frequency of C genotype of C3435T than un-adjuvant treatment group （68. 05% vs 48. 35%, P〈0. 01 ）. The frequency of G2677TA polymorphisms was of no significant difference between the two group recipients （P 0. 05）. As to non-adjuvant treatment recipients, the mean Tac DID required and C/D were not significantly different among various polymorphisms of MDR1 G2677T/A and C3435T or various haplotypes （P〉0. 05）. During A follow-up period of 4 years, 13 recipients suffered graft dysfunction in which 84. 6% （ 11 / 13） carried 3435C genotype （P〉0. 05 ）. Conclusion The frequency of MDR1 C3435T polymorphisms in RTRs is high in the recipients given adjuvant treatment to raise Tac concentrations. Recipients with 3435C genotype were prone to graft dysfunction.