肾移植患者的多药耐药基因外显子26基因型与术后他克莫司用量的关系

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。

Relationship between MDR1 exon 26 genotype and dosage of FK506 and acute rejection following renal transplantation

Objective To evaluate whether the MDR1 exon 26 genotype is associated with the dosage of FK506 and acute rejection in renal transplant patients. Methods One hundred and six patients who administrated FK506 after renal transplantation were retrospectively analyzed. The patients were investigated for MDR1 genotype determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assays. According to the genotype, the patients were divided into 3 subgroups, wild homozygous-CC, mutant homozygous-TT and heterozygous-CT. At 3rd, 6th and 12th month after renal transplantation, enzyme-linked immunosorbent assay (ELISA) was used to measure the FK506 whole blood concentration. Whole blood FK506 concentration per dose/kg/day and acute rejection within one month postoperation were compared among 3 subgroups. Results Of the 106 patients, 32 (30.2 %), 44 (41.5 %) and 30 (28.3 %) were carriers of CC, CT, TT in MDR1 exon 26, respectively. The whole blood FK506 concentration per dose/kg/day for patients with CC was remarkably lower that that of the patients with either CT or TT (P<0. 01), and there was a significant difference in whole blood FK506 concentration per dose/kg/day between patients with CT and those with TT (P<0. 05), the ratio with CT less than that of TT. The incidence of acute rejection in the patients expressing CC was higher than that in the patients expressing CT and TT (P< 0.05). No difference was found in the incidence of acute rejection between patients carrying CT and those expressing TT. Conclusions Compared to patients with CT and TT, patients with CC had got a higher risk of acute rejection and should receive a higher dosage of FK506 to achieve similar blood concentration. To know the MDR1 exon 26 genotype is advantage to guide immunosuppressant individual-ization and decrease the acute rejection post transplantation.