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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 |
| TITLE： | |
| 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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