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

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

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(C_(0)/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(C_(0))。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C_(0)/D和IPV的影响。结果:对于供者CYP3A4多态性,CYP3A4表达组他克莫司C_(0)/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C_(0)/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C_(0)/D,对他克莫司IPV没有影响。

Objective:To investigate the effectof donors′and recipients′CYP3A4 polymorphisms on tacrolimus concentration to dose ratio(C_(0)/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(C_(0))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 C_(0)/D and IPV in patients with different genotypes was analyzed.Results:For the donors′CYP3A4 polymorphism,tacrolimus C_(0)/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 C_(0)/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 C_(0)/D for infant patients with LDLT in the early postoperative period,but has no effect on tacrolimus IPV.