成人肝移植供受体CYP3A5基因分型对术后他克莫司临床个体化用药的应用价值探讨

Application discussion of donor and recipient CYP3A5 genotyping in clinical individualized drug use of tacrolimus after operation in adult liver transplantation

目的探讨成人肝移植供受体CYP3A5基因分型与术后他克莫司药物代谢的关系。方法回顾性收集天津市第一中心医院2018年7月至2019年6月期间施行的肝移植的供受体各98例为研究对象,术前收集肝移植受体和供体血,通过PCR法检测供受体的CYP3A5基因型,并收集术后1、2、3及4周的他克莫司浓度/剂量比。结果在98例肝移植供受体的CYP3A5基因分型中,均以GG型最多、AA型最少,且等位基因分布符合遗传规律,差异无统计学意义(P>0.05)。术后1、2、3及4周时,不管是在供体还是在受体中,3种基因型组的他克莫司浓度/剂量比两两比较差异均有统计学意义(P<0.05),GG型最高,AA型最低。联合供体和受体的基因型进行联合分组分析,结果表明,术后1、2、3及4周时,A*/A*、A*/GG、GG/A*和GG/GG组的他克莫司浓度/剂量比两两比较差异均有统计学意义(P<0.05),GG/GG型最高,A*/A*型最低。结论供受体的CYP3A5基因分型可以影响受体肝移植术后他克莫司的血药浓度,CYP3A5 GG基因型比其他基因型更容易达到目标血药浓度,检测肝移植患者供受体CYP3A5基因型可以为受体肝移植术后他克莫司的个体化治疗提供参考。

Objective To investigate the relationship between the CYP3A5 genotyping and the drug metabolism of tacrolimus after operation in adult liver transplantation.Methods Ninety-eight adult patients with liver transplantation in Tianjin First Center Hospital were selected as subjects.The blood samples of liver transplantation recipients and donor were collected before operation,and then tested the CYP3A5 genotyping by PCR method.The weekly body mass,tacrolimus dose,and drug valley concentration of the patients were monitored in 1,2,3,and 4 weeks after operation,to calculate the tacrolimus concentration/dose ratio.And then compared the effects of different genotyping of donor and receptors on tacrolimus concentration/dose ratio.Results In the CYP3A5 genotyping of 98 patients with liver transplantation and the corresponding donors,GG type was the most and AA type was the least,the distribution of alleles was in accordance with the genetic law,and the difference was not statistically significant(P>0.05).According to the donor genotype,the results showed that there was a significant correlation between tacrolimus concentration/dose ratio and donor or recipients CYP3A5 genotype at 1,2,3,and 4 weeks after liver transplantation,and there was significant difference among the three groups(P<0.05):GG>AG>AA.According to the combined grouping of donor and receptor genotype,the results showed that there was significant difference in tacrolimus concentration/dose ratio among A*/A*,A*/GG,GG/A*,and GG/GG group(P<0.05),while there was significant difference in tacrolimus concentration/dose ratio between GG/GG and A*/A*group(P<0.01),the tacrolimus concentration/dose ratio was highest in GG/GG group and lowest in A*/A*group.Conclusions The CYP3A5 genotyping of the recipient and donor can affect the blood concentration of tacrolimus after liver transplantation,and the CYP3A5 GG genotype is more likely to reach the target plasma concentration than the other genotypes,that the detection of donor and recipient CYP3A5 genotype in patients with liver transplantation can provide a reference for individualized treatment of tacrolimus after liver transplantation.