基于CYP3A5多态性的肾移植他克莫司个体化用药  

Personalized Tacrolimus medication in renal transplant recipients based on CYP3A5 gene polymorphism

作　　者：庞新路[1] 丰贵文[1] 尚文俊[1] 刘磊[1] 李金锋[1] 丰永花[1] 谢红昌[1] 

机构地区：[1]郑州大学第一附属医院肾移植科,河南郑州450052

出　　处：《现代泌尿外科杂志》2014年第5期294-296,307,共4页Journal of Modern Urology

摘　　要：目的研究基于CYP3A5基因多态性的肾移植术后他克莫司的个体化用药的可行性。方法采用等位基因特异扩增法对127例肾移植术后患者进行CYP3A5基因分型,CYP3A5*1/*1和CYP3A5*1/*3患者为高剂量组共66例:起始剂量0.12mg/(kg·d),1月时减至约0.1mg/(kg·d),1年时减至约0.03mg/(kg·d)。CYP3A5*3/*3为低剂量组共61例,应用标准剂量组的2/3剂量。观察两组之间他克莫司谷浓度、移植肾排斥反应、肺部感染、肝功能、血糖等指标。结果 CYP3A5*1/*1患者19例,CYP3A5*1/*3患者47例,CYP3A5*3/*3患者61例。肾移植患者高剂量组与低剂量组1年内分别发生排斥反应5例,发生率分别为7.6%和8.2%(P>0.05)。肾移植患者高剂量组与低剂量组1年内分别发生肺部感染6例和5例,发生率分别为9.1%和8.2%(P>0.05)。高剂量组和低剂量组1月时空腹血糖浓度分别为(4.9±0.6)mmol/L和(4.1±1.2)mmol/L(P<0.05),1年时空腹血糖浓度分别为(4.2±1.2)mmol/L和(4.3±0.6)mmol/L(P>0.05)。血清谷丙转氨酶(ALT)1月时浓度分别为(39.0±10.2)和(24.0±6.2)U/L(P<0.05),1年时的血清ALT浓度分别为(29.0±7.5)和(26±5.1)U/L(P>0.05)。结论基于CYP3A5基因多态性的肾移植术后他克莫司的个体化用药切实可行,不增加排斥反应的风险可降低药物肝损害等副作用。Objective To investigate the feasibility of personalized Tacrolimus medication in renal transplant recipients based on CYP3A5 gene polymorphism. Methods The CYP3A5 genotype of 127 renal transplantation patients were examined with allele-specific amplification method. CYP3A5 ＊ 1/＊ 1 and CYP3A5 ＊ 1/＊ 3 patients were high-dose group： starting dose 0.12 mg/（kg · d）, in the end of first month reduced to about 0.1 mg/（kg · d） and reduced to about 0.05 mg/（kg · d） at the end of half a year. CYP3A5 ＊ 3/＊ 3 patients were the low-dose group： given two thirds of the standard dose. Tacrolimus trough concentration, graft rejection, pulmonary infection, liver function, blood sugar and other indicators were observed. Results There were 19 CYP3A5 ＊ 1/＊ 1, 47 CYP3A5 ＊ 1/＊ 3 and 61 CYP3A5 ＊ 3/＊ 3 patients respectively. The acute rejection rate of high-dose group and low-dose group were 7.6 % and 8.2% respectively in 1 year （P〉0.05）. The pulmonary infection rate of high-dose group and low-dose group were 9.2 % and 8.2% respectively at the end of 1 year （P〉0.05）. The glucose level of high-dose group and low- dose group were （4.9 ±0.6）mmol/L and （4.1 ± 1.2）mmol/L respectively at the end of one month （P±0.05）. The glucose level of high-dose group and low-dose group were （4.2±0.7）mmol/L and （4.3 ± 1.0） mmol/L respectively at the end of one year （P〉0.05）. The ALT of high-dose group and low-dose group were （39.0±10.2） U/L and （24.0±6.2）U/L respectively at the end of one month （P〈0.05）, and were （29.0±7.5）U/L and （26.0±5. I）U/L respectively at the end of one year （P〉0.05）. Conclusion Personalized Tacrolimus medication based on the CYP3A5 gene polymorphism is practicable in renal transplant recipients.

关 键 词：他克莫司 肾移植 CYP3A5 

分 类 号：R979.5[医药卫生—药品]