多药耐药基因多态性和单倍体对肾移植患者他克莫司血药浓度的影响

Influence of multidrug resistant gene polymorphisms and haplotype on blood concentration of tacrolimus in renal transplant patients

目的研究多药耐药基因(MDR1)单核苷酸多态性及单倍体对中国汉族肾脏移植人群术后稳定期与他克莫司(免疫抑制剂)血药浓度的关系。方法用基质辅助激光吸收电离子化-飞行时间质谱技术,分析63例肾移植患者的MDR1 exon12 C1236T、exon 21 G2677T/A、exon 26 C3435T的基因型,结合其口服他克莫司12 h后血药浓度,判断两者是否存在关联。结果 MDR1 C3435T基因多态性与他克莫司血药浓度/(剂量×体表面积)具有相关性,比值由小到大顺序:野生型纯合子<杂合子<突变型纯合子,差异具有统计学意义(P<0.05)。MDR1 C1236T、G2677T/A及单倍体型各组之间比较均无明显差异。结论中国汉族肾移植患者稳定期,MDR1 C3435T与他克莫司血药浓度的个体差异具有相关性。

Objective To evaluate retrospectively the effects of genetic polymorphisms in exon 12 C1236T , exon 21 and exon 26 C3435T of multidrug resistant gene（ MDR1 ） gene on blood concentration of tacroli- mus in Chinese renal transplant patients in stable stage after renal trans- plantation. Methods Time- of flight mass spectrometry was used to a- nalysis the target genetic polymorphisms from 63 Chinese Han patients af- ter renal transplantation. Concentration of tacrolimus was detected 12 h after oral application. Then the relationship between them was estimated. Results A correlation was found between the concentration /（ dose x surface area） ratio and the SNPS of C3435T （P 〈 0. 05 ） , the ratio in- creased as follows： wild -type homozygote 〈 heterozygote 〈 mutant ho- mozygote. No difference was found among the MDR1 G2677T/A, C1236T, haploid genotypes and the ratio. Conclusion It was demon- strates that genetic polymorphism of MDR1 C3435T is correlated with the whole blood concentration/＇（ dose x surface area） of tacrolimus in Chinese renal transplant patients in stable stage.