肝移植患者他克莫司血药浓度与细胞色素P450 3A5 1*3基因多态性的关系

目的研究细胞色素P450 3A5 1*3基因多态性对肝移植患者他克莫司(免疫抑制剂)血药浓度的影响,探讨他克莫司在不同个体间吸收、代谢差异的基因背景。方法观察150例肝移植术后常规使用他克莫司 吗替麦考酚酯胶囊 醋酸泼尼松三联免疫抑制治疗的成年患者,分别测定术后1、3、6个月和12月的他克莫司全血药浓度,采用等位基因特异PCR测定细胞色素P450 3A5 1*3基因多态性,比较不同基因型之间他克莫司的浓度/剂量比的差异。结果在口服相同剂量的他克莫司时,1个月内CYP3A5 1*1、CYP3A5 1*3和CYP3A5 3*3三种基因型的浓度/剂量比,差异不显著;但3个月后,差异显著;6个月和12个月的浓度/剂量比,差异非常显著。结论CYP3A5 1*3多态性与肝移植患者他克莫司血药浓度具有非常显著的相关性,携带等位基因1*1和1*3患者的血药浓度明显低于3*3纯合子患者。

Association of CYP 3A5 1*3 polymorphisms and tacrolimus concentration in liver transplant recipients

Objective To investigate the association of (cytochrome P450,CYP450)CYP450 3A5 1*3 polymorphisms and tacrolimus concentration in liver transplant recipients. Methods One hundred fifty liver transplant recipients using tacrolimus with mycophenolat mofetil and steroids were genotyped for CYP 3A5 1*3 by allele specific PCR. Dose-adjusted through levels were determined and correlated with corresponding genotype.Results At 3,6 and 12 month, the tacrolimus dose-adjusted through levels were higher in CYP3A5 3*3 patients( n=113) than in 1*3 plus1*1 patients (n=37,P< 0. 05, Mann-Whitney test) .Conclusion CYP 3A5 1*3 polymorphisms are associated with tacrolimus pharmacokinetics and dose requirements, patients with CYP3A5 3*3 genotype require less tacrolimus to reach target concentrations compared to those with CYP3A5 1*3 and CYP3A5 1*1 allele.