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、 |
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摘要: |
摘 要 目的:研究肺移植患者术后使用他克莫司1年CYP3A5、CYP3A4、ABCB1、POR*28基因多态性与他克莫司给药剂量(D)和 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2017年5月-2018年5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c0和D,并计算c0/D。收集受试者CYP3A5 (rs776746)、CYP3A4(rs2242480、rs28371759)、ABCB1(rs1045642、rs2032582、rs1128503)和POR*28(rs1057868)位点的基因型,对 基因多态性与D、c0/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)。维 持他克莫司c0在治疗窗范围内的条件下,受试者的CYP3A5(rs776746)和CYP3A4(rs2242480)基因型多态性对他克莫司的D、c0/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 CYP3A5(rs776746)和 CYP3A4 (rs2242480)两个位点分析受试者CYP3A代谢型发现,同时携带CYP3A5(rs776746)*1和CYP3A4(rs2242480)*1G等位基因的快 代谢型受试者与只携带 CYP3A5(rs776746)*1 或 CYP3A4(rs2242480)*1G 等位基因的正常代谢型受试者和不携带 CYP3A5
(rs776746)*1和CYP3A4(rs2242480)*1G等位基因的慢代谢受试者比较,D、c0/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CYP3A5(rs776746)和CYP3A4(rs2242480)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。
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ABSTRACT: |
ABSTRACT OBJECTIVE:To study the association between CYP3A5,CYP3A4,ABCB1 and POR*28 genetic polymorphisms and drug dosage(D)and steady blood concentration/dosage(c0/D)of tacrolimus in lung transplant recipients after one year of tacrolimus administration. METHODS:By retrospective analysis,a 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 administration,and c0/D was calculated. Recipients’genotypes of CYP3A5(rs776746), CYP3A4(rs2242480,rs28371759),ABCB1(rs1045642,rs2032582,rs1128503)and POR*28(rs1057868)were collected. The relationship between genetic polymorphism and D,c0/D was analyzed statistically. RESULTS:The genotype frequency in this study were all in accordance with Hardy-Weinberg equilibrium (P>0.05). While maintaining tacrolimus c0 within therapeutic range, genetic polymorphism of CYP3A5(rs776746)and CYP3A4(rs2242480)influenced D and c0/D of tacrolimus significantly(P< 0.05). There was no statistical significance in D or c0/D among different genotypes of other sites(P>0.05). There was statistical significance in D or c0/D among extensive metabolism type recipients with CYP3A5(rs776746)*1 and CYP3A4(rs2242480)*1G
alleles,normal metabolism type recipients with only CYP3A5 (rs776746) *1 or CYP3A4 (rs2242480) *1G alleles and poor
metabolism type recipients without CYP3A5(rs776746)*1 and CYP3A4(rs2242480)* 1G alleles(P<0.05)
. D of tacrolimus was the highest in extensive metabolism type recipient and the lowest in poor metabolism type recipient. CONCLUSIONS:The detection of genetic polymorphism of CYP3A5(rs776746)and CYP3A4(rs2242480)has guiding significance for individualized medication of tacrolimus after one year of tacrolimus administration.
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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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