MDR1基因多态性影响儿童肝移植术后早期他克莫司代谢  

Impact of secondary pulmonary hypertension on lung transplant outcome

作　　者：罗文辉 秦寅鹏 邵佳[2] 陈凡[3] 高伟[3] 张弋[2] Luo Wenhui;Qin Yinpeng;Shao Jia;ChenFan;Gao Wei;Zhang Yi(First Central Clinical College of Tianjin Melical University,Tianjin 300192,China;De partmentof Pharmacy,First Municipal Central Hospital,Tianjin 300192,China;Organ TransplantCenter,First Municipal Central Hospital,Tianjin 300192,China)

机构地区：[1]天津医科大学一中心临床学院,300192 [2]天津市第一中心医院药学部,300192 [3]天津市第一中心医院器官移植中心,300192

出　　处：《中华器官移植杂志》2020年第7期407-411,共5页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金(81803356);天津市第一中心医院科技基金(院CM201806);医学科学研究基金(YWJKJJHKYJJ-B16244)

摘　　要：目的探究儿童肝移植术后早期MDR1(C3435T)基因多态性对受者他克莫司代谢的影响,辅助临床个体化给药。方法收集天津市第一中心医院90例儿童肝移植供、受者术前血样,检测供、受者基因型。记录术后受者他克莫司剂量、血药浓度及相关人口学信息。根据供、受者CYP3A5基因型,将受者划分为4个亚组:R/D-S亚组、R-F/D-S亚组、R-S/D-F亚组和R/D-F亚组。从亚组水平比较不同MDR1基因型受者他克莫司谷浓度/日剂量(C0/D)值差异是否有统计学意义。结果肝移植术后第1周90例受者中MDR1基因TT型的C0/D值显著高于CC型和CT型受者(P<0.01)。R/D-S亚组术后第2周CT型的C0/D值显著大于CC型受者(P<0.05)。R/D-F亚组CT型的术后第2周(P<0.05)、第3周(P<0.01)C0/D值显著大于CC型受者。结论 MDR1(C3435T)基因CC型受者较CT和TT基因型受者代谢较快,相同日剂量,他克莫司血药浓度较低,不同MDR1基因型受者需要调整给药剂量。这种差异在CYP3A5快代谢亚组中更加明显,需要临床给予更多的关注,优化个体化给药方案,降低不良反应发生率并提高疗效。Objective To explore the effect of MDR1(C3435T)gene polymorphism on tacrolimus metabolism early after pediatric liver transplantation.Methods Preoperative blood samples of 90 donors and recipients of pediatric liver transplantation were collected and genotyped.According to the CYP3A5 genotype of donor/recipient,they were divided into four subgroups of recipient slow metabolism/donor slow metabolism(R/D-S),recipient fast metabolism/donor slow metabolism(R-F/D-S),recipient slow metabolism/donor fast metabolism(R-S/D-F)and recipient fast metabolism/donor fast metabolism(R/D-F).The values of concentration/daily dose(C0/D)of tacrolimus in patients with different MDR1 genotypes were compared at the subgroup level.Results The C0/D value of MDR1 TT recipients was significantly higher than that of CC/CT counterparts in the first week after liver transplantation(P<0.01).The C0/D value of CT recipients in R/D-S subgroup was significantly higher than that of CC counterparts in the 2nd week after operation(P<0.05).The C0/D value of CT recipients in R/D-F subgroup was significantly higher than that of CC counterparts in 2 weeks(P<0.05)and 3 weeks(P<0.01).Conclusions MDR1(C3435T)gene polymorphism in recipients affects tacrolimus metabolism.Recipients with CC genotype metabolize faster than those with CT/TT genotypes.And the same daily dose and tacrolimus blood concentration are lower.Recipients with different MDR1 genotypes need to adjust the dosage of tacrolimus.This difference is more obvious in CYP3A5 fast metabolic subgroup,more attention should be paid to optimizing individualizing dosage regimens,reducing the incidence of adverse reactions and improving the efficacy.

关 键 词：肝移植 他克莫司 基因多态性 

分 类 号：R726.5[医药卫生—儿科]