【摘要】 目的 探讨黄素单氧化酶1（FMO1）基因多态性（SNP）与肾移植患者术后初期他克莫司浓度的相关性。方法 以术后接受他克莫司+霉酚酸类药物+泼尼松三联免疫疗法的肾移植患者为研究对象，用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法对CYP3A5*3（rs776746）进行基因分型，用Agena Bioscience MassARRAY^? system对FMO1 rs10912675和rs7877的进行基因分型，术后第6～10天他克莫司全血稳态谷浓度（C₀）为临床治疗药物监测（TDM）数据，用SPSS软件分析各基因型与他克莫司剂量校正谷浓度（C₀/D）的相关性。结果 本试验共纳入176例患者。CYP3A5*1/*1及CYP3A5*1/*3型（CYP3A5表达型）患者的他克莫司C₀/D显著低于CYP3A5*3/*3型（CYP3A5非表达型）患者（P<0.001）。FMO1 rs10912675 CC型患者他克莫司C₀/D显著高于CT和TT型患者（P<0.05）;FMO1 rs7877 TT型患者他克莫司C₀/D显著高于CT和CC型患者（P<0.05）。按CYP3A5*3基因型分层后，在CYP3A5表达型患者中，FMO1 rs10912675 CC型患者他克莫司C₀/D显著高于CT和TT型患者（P<0.05）。结论 FMO1 rs10912675基因型与肾移植患者术后初期他克莫司浓度存在相关性，提示他克莫司也可能是FMO1酶的底物，并且该基因型也可能成为指导他克莫司个体化用药的新的参考依据。更多还原

【Abstract】 Objective To investigate the associations of flavincontaining monooxygenase 1（FMO1） polymorphisms with tacrolimus concentration in early post-renal transplant recipients.Methods Posttransplant patients treated with triple immunotherapy（mycophenolic acid+tacrolimus+prednisone） were included.CYP3A5*3 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method and FMO1（rs10912675 and rs7877） genotypes were detected by Agena Bioscience Mass ARRAY^?system.Steady state trough concentrations of tacrolimus on day 6-10after renal transplantation were collected from clinical data.Correlations between genetic polymorphisms and tacrolimus dose adjusted trough concentration（C₀/D） were analyzed by SPSS.Results A total of 176post-transplant patients were included.The C₀/D of tacrolimus in CYP3A5*1/*1 and CYP3A5*1/*3 carriers（CYP3A5 expressers）was significantly lower than that in CYP3A5*3/*3（CYP3A5nonexpressers）（P <0.05）.A considerably higher C₀/D of tacrolimus was found in FMO1 rsl0912675 CC carriers than that in CT and TT carriers（P<0.05）.FMOl rs7877 TT carriers had a higher C₀/D of tacrolimus level compared with CT and CC carriers（P<0.05）.After stratification by CYP3A5*3 genotype,a higher C₀/D of tacrolimus were observed in FMO1 rs10912675 CC carriers than that in CT and TT carriers in CYP3A5 expressers（P<0.05）.Conclusion The results illustrated that FMO1 rs10912675 polymorphisms were associated with tacrolimus concentrations,suggesting that tacrolimus may be a substrate of FMO1 and genotyping for this SNP may provide a g a new reference for clinical dose prediction of tacrolimus.更多还原