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目的研究肾移植患者的多药耐药基因(MDR1)外显子26(exon26)的基因型与术后他克莫司(FK506)用量的关系。方法回顾106例肾移植术后常规使用FK506患者的临床资料。肾移植患者MDR1 exon26基因分型的方法为:提取患者的DNA,采用聚合酶链反应(PCR)扩增MDR1基因,检测限制性内切酶片段的多态性(RFLP)。根据MDR1 exon26基因分型将患者分为CC、CT和TT 3组。检测各组患者肾移植后第3、6和12个月的FK506血药浓度,比较各组患者FK506血药浓度／FK506用量(μg·L-1／mg·kg-1·d-1)的比值及术后1个月内的急性排斥反应发生率。结果受者经MDR1 exon26基因分型示:CC型32例(30．2％),TT型30例(28．3％),CT型44例(41．5％)。CC型患者FK506血药浓度／FK506用量的比值明显低于CT型和TT型(P<0．01),而CT型患者又低于TT型(P<0．05)。CC型患者的排斥反应发生率明显高于CT和TT型(P<0．05),CT与TT型比较,差异无统计学意义(P>0．05)。结论MDR1 exon26 CC型的患者与CT或TT型比较,需服用更高剂量的FK506才能取得与CT或TT型相似的血药浓度。因此,了解患者的MDR1 exon26基因型有利于指导患者肾移植术后个体化用药。
Objective To study the relationship between the genotype of exon26 and the dosage of postoperative tacrolimus (FK506) in MDR1 patients. Methods The clinical data of 106 patients with conventional FK506 after renal transplantation were retrospectively reviewed. MDR1 exon26 genotyping in renal transplant patients by extracting the patient’s DNA, using polymerase chain reaction (PCR) amplification of MDR1 gene, restriction fragment analysis of polymorphisms (RFLP). Patients were divided into CC, CT and TT 3 groups according to MDR1 exon26 genotyping. The plasma concentrations of FK506 at 3, 6 and 12 months after renal transplantation were measured in each group. The plasma concentrations of FK506 / FK506 (μg · L-1 / mg · kg-1 · d-1) Ratio and incidence of acute rejection within 1 month after operation. Results The genotypes of MDR1 exon26 in recipients showed that there were 32 cases of CC (30.2%), 30 cases of TT (28.3%) and 44 cases (41.5%) of CT. The ratio of plasma concentration of FK506 / FK506 in CC patients was significantly lower than that of CT and TT (P <0.01), while that of CT was lower than that of TT (P <0.05). The incidence of rejection in CC patients was significantly higher than that in CT and TT (P <0.05). There was no significant difference between CT and TT (P> 0.05). CONCLUSION: Patients with MDR1 exon26 type CC require a higher dose of FK506 to achieve similar plasma concentrations than those with CT or TT compared with those with CT or TT. Therefore, understanding the patient’s MDR1 exon26 genotype is helpful for guiding the individualized treatment of patients after kidney transplantation.