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目的探讨肾移植术后患者的多药耐药基因(MDR1)外显子21(exon21)和26(exon26)的基因多态性对免疫抑制剂他克莫司(FK506)血药浓度的影响。方法采用聚合酶链反应(PCR)和限制性内切片段多态性(RFLP)的方法对86例肾移植术后的患者进行MDR1基因分型。使用酶联免疫吸附法(ELISA)测定患者在术后不同时间的FK506血药浓度。比较不同基因型之间FK506血药浓度与每公斤体重的剂量比值的差异。结果在86例患者中,exon21中GG型为26个(30.2%),GT型为35个(40.7%),TT型为25个(29.1%);exon26中CC型为26个(30.2%),CT型为37个(43.0%),TT型为23个(26.8%)。MDR1 exon26 C3435T与MDR1 exon21 G2677T之间存在着明显的连锁不平衡。GG型患者的比值明显低于CT型和TT型患者,而GT型患者又低于TT型患者,差异均具有统计学意义(均P<0.05);同样CC型患者的比值明显低于CT型和TT型患者,而CT型患者又低于TT型患者,差异均具有统计学意义(均P<0.05)。结论在肾移植患者中MDR1基因多态性与FK506血药浓度具有相关性。GG型和CC型患者拟取得相似的血药浓度要比GT或TT型和CT或TT型患者服用更高剂量的FK506。了解患者的MDR1基因型,有利于肾移植术后FK506个体化应用。
Objective To investigate the effect of exon21 and 26 (exon26) gene polymorphism of multidrug resistance gene (MDR1) on the plasma concentration of immunosuppressant (FK506) in renal transplant recipients. Methods MDR1 genotyping was performed in 86 patients after renal transplantation by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). FK506 plasma concentrations were measured at different times after surgery using enzyme-linked immunosorbent assay (ELISA). Differences in the ratio of plasma concentrations of FK506 to doses per kilogram of body weight were compared between different genotypes. RESULTS: Of the 86 patients, 26 (30.2%) had type GG in exon21, 35 (40.7%) in type GT, 25 (29.1%) in TT and 26 (30.2%) in type 2 , 37 (43.0%) for CT and 23 (26.8%) for TT. There is a clear linkage disequilibrium between MDR1 exon26 C3435T and MDR1 exon21 G2677T. The ratio of GG patients was significantly lower than that of CT patients and TT patients, while that of GT patients was lower than that of TT patients (all P <0.05). Similarly, the ratio of CC patients was significantly lower than that of CT patients And TT patients, while CT patients were lower than TT patients, the differences were statistically significant (P <0.05). Conclusion The MDR1 gene polymorphism in renal transplant patients is correlated with the concentration of FK506. Patients with GG and CC are expected to receive similar doses of plasma at higher doses of FK506 than patients with GT or TT or CT or TT. Understanding the patient’s MDR1 genotype facilitates the individualized use of FK506 after renal transplantation.