肺移植患者术后使用他克莫司 1 年 CYP3A5、CYP3A4、ABCB1、
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篇名: 肺移植患者术后使用他克莫司 1 年 CYP3A5、CYP3A4、ABCB1、
TITLE:
摘要:
摘 要 目的研究肺移植患者术后使用他克莫司1CYP3A5CYP3A4ABCB1POR*28基因多态性与他克莫司给药剂量D稳态血药浓度/给药剂量比值c0/D的关系方法采用回顾性分析方法选取20175-20185月期间在中日友好医院接受 肺移植术的46例受试者为研究对象统计受试者术后使用他克莫司1年后他克莫司的c0D并计算c0/D收集受试者CYP3A5 rs776746)、CYP3A4rs2242480rs28371759)、ABCB1rs1045642rs2032582rs1128503POR*28rs1057868位点的基因型基因多态性与Dc0/D的关系进行统计学分析结果本研究中涉及位点的基因型频率均符合Hardy-Weinberg平衡P>0.05)。持他克莫司c0在治疗窗范围内的条件下受试者的CYP3A5rs776746CYP3A4rs2242480基因型多态性对他克莫司的Dc0/D 有显著影响P<0.05);其他位点各基因型之间的 D
c0/D 差异均无统计学意义P>0.05)。联合 CYP3A5rs776746CYP3A4 rs2242480两个位点分析受试者CYP3A代谢型发现同时携带CYP3A5rs776746*1CYP3A4rs2242480*1G等位基因的快 代谢型受试者与只携带 CYP3A5rs776746*1 CYP3A4rs2242480*1G 等位基因的正常代谢型受试者和不携带 CYP3A5
rs776746*1CYP3A4rs2242480*1G等位基因的慢代谢受试者比较Dc0/D差异具有统计学意义P<0.05),其中快代谢型受 试者的他克莫司D最高慢代谢型受试者的他克莫司D最低结论检测CYP3A5rs776746CYP3A4rs2242480基因多态性 对肺移植患者术后使用他克莫司1年后他克莫司的个体化给药具有指导意义
ABSTRACT:
ABSTRACT OBJECTIVETo study the association between CYP3A5CYP3A4ABCB1 and POR*28 genetic polymorphisms and drug dosageDand steady blood concentration/dosagec0/Dof tacrolimus in lung transplant recipients after one year of tacrolimus administration. METHODSBy retrospective analysisa total of 46 recipients who underwent lung transplantation in China-Japan Friendship Hospital during May 2017-May 2018 were selected. The c0 and D of tacrolimus were measured and collected after one year of tacrolimus administrationand c0/D was calculated. Recipientsgenotypes of CYP3A5rs776746), CYP3A4rs2242480rs28371759),ABCB1rs1045642rs2032582rs1128503and POR*28rs1057868were collected. The relationship between genetic polymorphism and Dc0/D was analyzed statistically. RESULTSThe genotype frequency in this study were all in accordance with Hardy-Weinberg equilibrium P>0.05. While maintaining tacrolimus c0 within therapeutic rangegenetic polymorphism of CYP3A5rs776746and CYP3A4rs2242480influenced D and c0/D of tacrolimus significantlyP0.05. There was no statistical significance in D or c0/D among different genotypes of other sitesP>0.05. There was statistical significance in D or c0/D among extensive metabolism type recipients with CYP3A5rs776746*1 and CYP3A4rs2242480*1G
allelesnormal metabolism type recipients with only CYP3A5 rs776746*1 or CYP3A4 rs2242480*1G alleles and poor
metabolism type recipients without CYP3A5rs776746*1 and CYP3A4rs2242480* 1G allelesP<0.05
. D of tacrolimus was the highest in extensive metabolism type recipient and the lowest in poor metabolism type recipient. CONCLUSIONSThe detection of genetic polymorphism of CYP3A5rs776746and CYP3A4rs2242480has guiding significance for individualized medication of tacrolimus after one year of tacrolimus administration.
期刊: 2020年第31卷第1期
作者: 杜雯雯,王晓星,张 丹,李朋梅
AUTHORS: DU Wenwen,WANG Xiaoxing,ZHANG Dan,LI Pengmei
关键字: 他克莫司;基因多态性;肺移植;术后1年;血药浓度;给药剂量;CYP3A5;CYP3A4;ABCB1;POR*28
KEYWORDS: Tacrolimus;Geng polymorphism;Lung transplant;One year after operation;Blood concentration;Drug dosage;
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