肾移植中他克莫司的血药浓度与多药耐药基因多态性的关系  

Relationship between MDR1 gene polymorphism and blood concentration of tacrolimus in renal transplant patients

作　　者：王玮[1] 张小东[1] 马麟麟[1] 胡小朋[1] 张鹏[1] 王勇[1] 吕月平[2] 管德林[3] 

机构地区：[1]首都医科大学附属北京朝阳医院泌尿科,100020 [2]首都医科大学基础医学研究中心 [3]清华大学附属北京华信医院泌尿科

出　　处：《中华医学杂志》2005年第46期3277-3281,共5页National Medical Journal of China

摘　　要：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 relationship between MDR1 exon 21 and exon 26 polymorphism and whole blood concentration of tacrolimus （FKS06） in renal transplant patients, Methods Blood samples were collected from 86 renal transplant patients who received FK506 peri-operationally, PCR-RELP was used to determine the MDR1 genotype. The patients were divided into 3 subgroups for every position： GG, GT, and TT in exon 21; and CC, CT, and TT in exon 26. Three, six, and twelve months after the transplantation ELISA was used to measure the whole blood concentration of FKS06. The FKS06 concentrations standardized by dosage and body weight （FKS06 concentration per dose/kg） were compared among the 3 subgroups within the MDR1 exon 21 and exon 26 groups. Results Of the 86 patients 26 （30.2%）, 35 （40.7%）, and 25 （29.1%） were carriers of GG, GT, and TT in exon 21, and 26 （30. 2% ） , 35 （40. 7% ） , and 23 （26. 8% ） were carriers of CC, CT, and TT in exon 26. MDR1 exon 26 C3435T was in significant linkage disequilibrium with MDR1 exon 21 G2677T. Three, six, and twelve months after the transplantation a significant correlation between the whole blood FKS06 concentration per dose/day and MDR1 exon 21 and exon 26 genotypes. For exon 21 there were significant differences among the 3 subgroups （ all P 〈 0. 01 ）. The ratio for the patients with GG was remarkably lower than that of those with GT and TT, and the ratio with GT was also lower than the patients with TT （P 〈0. 05）. For exon 26, there was also a significant difference among the 3 subgroups （ all P 〈0. 01 ）. The ratio for the patients with CC was remarkably lower than those of the patients with CT and TT, and the ratio of CT was also lower than that of TT （ P 〈 0. 05 ）. Conclusions The MDR1 gene polymorphism is correlated with the whole blood concentration of FKS06. To obtain the similar blood concentration of FKS06, the patients with GG and CC should take the drug at a higher dose than those with Ct and Tr.

关 键 词：抗药性 多药 P-糖蛋白 多态性 单核苷酸 他克莫司 肾移植 

分 类 号：R699[医药卫生—泌尿科学]