受者CYP3A5基因多态性对肾移植术后早期血他克莫司浓度的影响  

Effect of CYP3A5 polymorphism on tacrolimus concentration during early period after kidney transplantation in recipients

作　　者：滕立臣[1] 王长希[1] 陈立中[1] 李嘉丽[2] 费继光[1] 邓素雄[1] 邱江[1] 李军[1] 陈国栋[1] 

机构地区：[1]中山大学附属第一医院器官移植科,广州510080 [2]中山大学药学院临床药理研究所

出　　处：《中华器官移植杂志》2009年第5期261-263,共3页Chinese Journal of Organ Transplantation

摘　　要：目的研究细胞色素P4503A酶系中CYP3A5基因多态性对肾移植术后早期血他克莫司（Tac）浓度的影响。方法90例肾移植患者均采用Tac、霉酚酸酯和泼尼松预防排斥反应。患者于术后第2～3天开始口服Tac，初始剂量为0．15mg·kg^-1·d^-1。用酶联免疫吸附试验法测定血Tac浓度谷值，记录术后1个月内的数据，并据此调整药物剂量，使Tac浓度谷值维持在5～10μg／L。根据患者服用Tac的剂量，计算浓度／剂量比值（C／D），并记录患者每日血肌酐的下降速度。用聚合酶链反应-限制性片段长度多态性法进行CYP3A5基因多态性的检测。结果CYP3A5基因型为野生型纯合子（^＊1／^＊1型）者9例，突变型纯合子（^＊3／^＊3型）者41例，突变型杂合子（^＊1／^＊3）者40例。^＊3／^＊3型者的初次Tac浓度谷值为（9．8±3．1）μg／L，明显高于基因型为^＊1／^＊1型和^＊1／^＊3型者（P〈0．05，P〈0．05）。术后2周内，^＊3／^＊3型者的C／D最高，^＊1／^＊3型者次之，^＊1／^＊型者最低，前者与后二者相比较，差异有统计学意义（P〈0．05，P〈0．05）。术后第1周，^＊3／^＊3型者血肌酐的下降速度最快，每天下降（127．4±59．6）μmol／L，高于^＊1／^＊3型者和^＊1／^＊1型者（P〈0．05，P〈0．05）。结论CYP3A5基因型对肾移植术后1个月内血Tac的浓度谷值有一定影响。Objective To investigate effect of cytochrome P-450 CYP3A5 polymorphism on trough level of tacrolimus during early stage after kidney transplantation in recipients. Methods All of 90 recipients were treated with tacrolimus in combination with mycophenolate mofetil and predonisone for preventing reject episode after surgery. Tacrolimus with a dose of 0. 15 mg.kg^-1 .d^-1 was initiated at second or third day post-transplantation. The though levels of tacrotimus assayed by ELISA were observed for one month after transplantation, and tacrolimus dosages were frequently adjusted to make its range from 5-10 g/L. The ratio of concentration-to-dose （C/D） and decreasing rate of serum creatinine per day were recorded. PCR-RFPL method was used for analyzing occurrence of CYP3A5 polymorphisms. Results The recipients with wild homozygote （CYP3A5＆＊ 1/^＊ 1）, mutant homozygote （CYP3A5^＊ 3/^＊ 3）, and mutant heterozygote （CYP3A5^＊ 1/^＊ 3） were 9, 41 and 40 cases, respectively. The initial trough level （9. 8 ± 3. 1 g/L） in patients with CYP3A5^＊ 3/^＊ 3 was markedly higher than that in patients with CYP3A5^＊ 1/^＊ 1, and CYP3A5^＊ 1/^＊ 3 （both P〈0. 05）. Concentration-to-dose ratio among patients with different CYP3A5 alleles was in the order of ^＊ 3/^＊ 3〉 ^＊1/^＊ 3〉^＊ 1/^＊ 1 for the first two weeks after operation, which was markedly higher in CYP3A5 ^＊ 3/^＊ 3 patients than that in patients with latter two genotypes （both P〈0. 05）. The serum creatinine decreasing rate （127. 4 ± 59. 6 μmol. L^-1 . d^-1） in CYP3A5^＊ 3/^＊ 3 patients was higher than that in CYP3A5^＊ 1/^＊ 1 and CYP3A5 ^＊ 1/^＊ 3 patients in the first week post-transplantation （both P〈0. 05）. Conclusion CYP3A5 genotypes can affect the trough level of tarcrolimus during the first month post-transplantation in recipients.

关 键 词：细胞色素P450 CYP3A 他克莫司 血药浓度 基因 肾移植 

分 类 号：R686[医药卫生—骨科学]