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  

Influence of CYP3A5*3 Genetic Polymorphism on Blood Concentration of Tacrolimus and Renal Function in Renal Transplant Recipients during the Stable Period

作　　者：卫泽武[1] 王学彬[1] 张文文 杨云云[1] 高丽红[1] 马多玲[1] 肖成武[2] 王卓[1] 高申[1] 

机构地区：[1]上海长海医院药学部,上海200433 [2]上海长海医院泌尿外科,上海200433

出　　处：《中国药房》2018年第2期183-187,共5页China Pharmacy

基　　金：上海市卫生计生系统重要薄弱学科建设计划项目(No.沪卫计科教[2016]41号-2016ZB0303-01)

摘　　要：目的:探讨细胞色素P_(450)(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。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 TALC 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 polyrnorphism with TAC C/D value and Scr level was determined by Kruskal Wallis Hor Mann-Whitney U assay. RESULTS： Among 98 renal transplant recipients, there were 9 cases of CYP3A5＊3 ＊i/＊i （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/＊3and ＊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 rec

关 键 词：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 

分 类 号：R969.3[医药卫生—药理学] R699.2[医药卫生—药学]