CYP3A4多态性对活体肝移植患儿术后早期他克莫司浓度/剂量比和个体内变异度的影响

目的:探讨供、受者CYP3A4多态性对活体肝移植（LDLT）患儿术后1个月内他克莫司浓度/剂量比（C0/D）和个体内变异度（IPV）的影响。方法:收集77例活体肝移植患儿，化学发光免疫分析法测定他克莫司谷浓度（C0）。检测供、受者CYP3A4*18B基因型，根据患者至少携带一个CYP3A4*1基因将患者分为两组，即CYP3A4表达组（EX，CYP3A4*1/*1或CYP3A4*1/*18B）和CYP3A4非表达组（NEX，CYP3A4*18B/*18B）。分析CYP3A4*18B多态性对不同基因型患者他克莫司C0/D和IPV的影响。结果:对于供者CYP3A4多态性，CYP3A4表达组他克莫司C0/D在术后第1周（Z=-4.694，P＜0.001）、第2周（Z=-4.469，P＜0.01）和第3周（Z=-2.205，P＜0.05）均显著低于CYP3A4非表达组；对于受者CYP3A4多态性，CYP3A4表达组他克莫司C0/D在术后第1周（Z=-4.976，P＜0.001）和第2周（Z=-3.054，P＜0.01）均显著低于CYP3A4非表达组。此外，供、受者CYP3A4表达组与CYP3A4非表达组他克莫司IPV均无差异（均P>0.05）。结论:CYP3A4多态性影响LDLT患儿术后早期他克莫司C0/D，对他克莫司IPV没有影响。

Effect of CYP3A4 polymorphism on tacrolimus concentration to dose ratio and intra-patient variability in the early postoperative period for infant patients with living donor liver transplantation

Objective: To investigate the effectof donors′ and recipients′ CYP3A4 polymorphisms on tacrolimus concentration to dose ratio（C0/D） and intra-patient variability（IPV） within one month for infant patients with living donor liver transplantation（LDLT）. Methods: A total of 77 infant patients with LDLT were collected. Tacrolimus trough concentration（C0） was determined by chemiluminescent microparticle immunoassay.The donors′ and recipients′ CYP3A4*18B genotypes were detected.According to individuals with at least one CYP3A4*1 allele，patients were divided into two groups including CYP3A4 expressers（EX，CYP3A4*1/*1 or CYP3A4*1/*18B） and CYP3A4 non-expressers（NEX，CYP3A4*18B/*18B）.The effect of CYP3A4*18B polymorphism on tacrolimus C0/D and IPV in patients with different genotypes was analyzed. Results: For the donors′ CYP3A4 polymorphism，tacrolimus C0/D in CYP3A4 expressers was significantly lower than that in CYP3A4 non-expressers in the first week（Z=-4.694，P＜0.001），second week（Z=-4.469，P＜0.01），and third week（Z=-2.205，P＜0.05） after transplantation. For the recipients′ CYP3A4 polymorphism, tacrolimus C0/D in CYP3A4 expressers was significantly lower than that in CYP3A4 non-expressers in the first week（Z=-4.976，P＜0.001） and second week（Z=-3.054，P＜0.01） after transplantation. In addition, there was no difference in tacrolimus IPV between CYP3A4 expressers and CYP3A4 non-expressers（all P>0.05）. Conclusion: The CYP3A4 polymorphism has an effect on tacrolimus C0/D for infant patients with LDLT in the early postoperative period，but has no effect on tacrolimus IPV.