CYP3A5*3基因多态性对稳定期肾移植受者他克莫司血药浓度及肾功能的影响
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篇名: CYP3A5*3基因多态性对稳定期肾移植受者他克莫司血药浓度及肾功能的影响
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摘要: 目的:探讨细胞色素P450(CYP)3A5*3(rs776746)基因多态性对稳定期肾移植受者他克莫司(TAC)血药浓度和肾功能的影响。方法:选择1995年3月-2014年12月于我院行肾移植术并于术后接受以TAC为基础的三联抗排斥方案(TAC+麦考酚钠+醋酸泼尼松)治疗且行定期门诊随访的稳定期肾移植受者98例,收集其2016年1-12月的随访信息。采用化学发光微粒子免疫分析法检测肾移植受者的TAC血药谷浓度,并计算经体质量和日剂量校正的标准化血药浓度(C/D)值;采用干化学法检测血肌酐(Scr)水平;采用聚合酶链反应-限制性片段长度多态性法、直接测序法检测CYP3A5*3基因分型。采用Kruskal Wallis H检验或Mann-Whitney U检验分析CYP3A5*3基因多态性与TAC的C/D值、Scr水平的相关性。结果:98例肾移植受者中,CYP3A5*3 *1/*1(AA)、*1/*3(AG)、*3/*3(GG)型分别有9、37、52例,各基因型频率分别为9.18%、37.76%、53.06%,均符合Hardy-Weinberg遗传平衡(P>0.05)。不同基因型受者TAC血药谷浓度比较,差异无统计学意义(P>0.05);TAC剂量和C/D值比较,差异均有统计学意义(P<0.05)。其中,CYP3A5*3 *3/*3型受者TAC剂量显著低于*1/*3、*1/*1型受者,且*1/*3型受者显著低于*1/*1型受者;*3/*3型受者TAC的C/D值显著高于*1/*3、*1/*1型受者,且*1/*3型受者显著高于*1/*1型受者,差异均有统计学意义(P<0.05)。不同基因型受者Scr水平比较,差异无统计学意义(P>0.05)。结论:CYP3A5*3基因多态性对我国稳定期肾移植受者TAC的血药浓度有显著影响,*3等位基因携带者TAC的C/D值更高,且每日所需的TAC剂量更低;但CYP3A5*3基因多态性可能与其Scr水平无关。
ABSTRACT: OBJECTIVE: To investigate the influence of CYP3A5*3(rs776746) genetic polymorphism on blood concentration of tacrolimus (TAC) and renal function in renal transplant recipients during the stable period. METHODS: A total of 98 renal transplant recipients during the stable period receiving TAC-based triple anti-rejection scheme (TAC+sodium mycophenol+prednisone acetate) after surgery and regular follow-up were selected from our hospital during Jan. 1995-Dec. 2014. The follow-up information during Jan.-Dec. 2016 was also collected. Trough concentration of TAC in renal transplant recipients was determined by chemiluminescence microparticle immuno assay. Standard blood concentration (C/D) was calculated after corrected with body weight and daily dose. Scr level was detected with dry chemistry method. CYP3A5*3 genotype was detected by PCR-RFLP and direct sequencing. The relationship of CYP3A5*3 genetic polymorphism with TAC C/D value and Scr level was determined by Kruskal Wallis H or Mann-Whitney U assay.  RESULTS: Among 98 renal transplant recipients, there were 9 cases of CYP3A5*3 *1/*1(AA) genotype, 37 cases of *1/*3(AG) genotype and 52 cases of *3/*3(GG)genotype. The gene frequencies were 9.18%, 37.76%, 53.06%, which were all in line with Hardy-Weinberg equilibrium (P>0.05). There was no statistical significance in trough concentration of TAC among different genotypes (P>0.05). There was statistical significance in TAC dose and C/D value among different genotypes (P>0.05). TAC dose of CYP3A5*3 *3/*3 genotype recipients was significantly lower than those of *1/*3 and *1/*1 genotype recipients; that of *1/*3 genotype recipients was significantly lower than that of *1/*1 genotype recipients. C/D value of *3/*3 genotype recipients was significantly higher than those of *1/*3 and *1/*1 genotype recipients; that of *1/*3 genotype recipients was significantly higher than that of *1/*1 genotype recipients, with statistical significance (P<0.05). There was no statistical significance in Scr levels among different genotypes (P>0.05). CONCLUSIONS: CYP3A5*3 genetic polymorphism significantly influences blood concentration of TAC in renal transplant recipients during the stable period, and *3 allele carriers have higher C/D values and need smaller TAC daily dose. CYP3A5*3 genetic polymorphism may be not associated with Scr level.
期刊: 2018年第29卷第2期
作者: 卫泽武,王学彬,张文文,杨云云,高丽红,马多玲,肖成武,王卓,高申
AUTHORS: WEI Zewu,WANG Xuebin,ZHANG Wenwen,YANG Yunyun,GAO Lihong,MA Duoling,XIAO Chengwu,WANG Zhuo,GAO Shen
关键字: CYP3A5*3基因;基因多态性;他克莫司;稳定期;肾移植;血药浓度;肾功能
KEYWORDS: CYP3A5*3 gene; Genetic polymorphism; Tacrolimus; Stable period; Renal transplantation; Plasma concentration; Renal function
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