肺移植术后受体CYP3A5和白介素-10基因多态性与他克莫司个体化用药的关系  

Association of CYP3A5 and IL-10 Polymorphisms with the Individual Dosage Regimen of Tacrolimus in Lung Transplantation Recipients

作　　者：徐雯[1] 张晓庆[1] 樊军卫[2] 李玉平[1] 谢博雄[3] 舒萍[1] 

机构地区：[1]同济大学附属上海市肺科医院药剂科,上海200433 [2]上海交通大学附属第一人民医院普外科,上海200080 [3]同济大学附属上海市肺科医院胸外科,上海200433

出　　处：《中国药房》2015年第35期4931-4934,共4页China Pharmacy

基　　金：国家自然科学基金(青年基金)资助项目(No.81202609)

摘　　要：目的:探讨肺移植术后受体细胞色素P450(CYP)3A5和白介素(IL)-10基因多态性与他克莫司血药浓度/给药剂量(C/D)的关系。方法:利用Sequenom Mass Array i PLEX GOLD系统检测51例肺移植患者外周血CYP3A5 rs776746和IL-10 rs1800896位点单核苷酸多态性,分析基因多态性与他克莫司代谢表型C/D的相关性。结果:肺移植术后,受体CYP3A5 rs776746 GG基因型患者他克莫司C/D明显高于AA+AG型患者,差异有统计学意义(P<0.01)。在术后第1周和第2周受体IL-10 rs1800896 AA基因型患者他克莫司C/D明显高于AG基因型患者,差异有统计学意义(P<0.05)。联合分析这两个基因,携带快代谢等位基因数目多的患者他克莫司C/D明显低于不携带的患者,差异有统计学意义(P<0.01)。结论:联合检测受体CYP3A5 rs776746和IL-10rs800896基因型有助于指导他克莫司个体化用药。OBJECTIVE：To investigate the association of Cytochrome P4503 A family polypeptide 5 [（CYP）3A5] and IL-10 polymorphisms with the concentration/dose（C/D） ratio of tacrolimus in lung transplantation recipients. METHODS：CYP3A5 polymorphisms at rs774746 and IL-10 polymorphisms at rs1800896 from peripheral blood cell of 51 lung transplant recipients was detected by Sequenom Mass Array i PLEX GOLD system. The relationship between gene polymorphism and tacrolimus C/D ratio was analyzed. RESULTS：The tacrolimus C/D ratio of the recipients who carried CYP3A5 rs776746 GG genotype were higher than those with AA＋GG genotype,with statistical significance（P〈0.01）. The tacrolimus C/D ratio of the recipients who carried IL-10 rs1800896 AA genotype were higher than those with AG genotype during 1 week and 2 weeks after transplantation,with statistical significance（P〈0.05）. Combined analysis of these two genes,the tacrolimus C/D ratio of the recipients who carried more fast metabolic alleles were higher than those who didn＇t carry fast metabolic alleles,with statistical significance（P〈0.01）. CONCLUSIONS：Determination of recipients CYP3A5 at rs 776746 and IL-10 at rs800896 genotype may be performed prospectively to help individualizing tacrolimus dose regimen.

关 键 词：肺移植 他克莫司 细胞色素P4503A5 白介素-10 基因多态性 

分 类 号：R969.1[医药卫生—药理学]