肝移植术后受体他克莫司个体化用药与供体细胞色素P4503A亚家族多肽5和白细胞介素-18基因多态性的关系  

Association of donor cytochrome P450 3A family polypeptide 5 and interleulin-18 polymorphisms with the individual dosage regimen of tacrolimns in chinese liver transplantation recipients

作　　者：张晓庆[1] 王兆文[2] 陈达伟[2] 郭峰[2] 彭志海[2] 樊军卫[2] 

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

出　　处：《中华实验外科杂志》2013年第10期2073-2075,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金青年基金资助项目（81202609）;国家高技术研究发展计划（863计划）资助项目（2012AA021002）;上海交通大学医工交叉基金项目（YG2012MS05）

摘　　要：目的 探讨肝移植供体细胞色素P4503A亚家族多肽5（CYP3A5）和白细胞介素-18（IL-18）基因多态性与受体术后他克莫司血药浓度/给药剂量的关系.方法 应用测序技术检测84例肝移植患者供体CYP3A5 rs776746和IL-18rs5744247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（全血谷浓度/剂量比值,C/D,ng· ml-·mg-·kg-）的相关性.结果 肝移植术后,供体IL-18 rs5744247 GG＋ GC基因型患者他克莫司C/D值[（163.1±100.8）ng·ml-1.mg-1·kg-1]明显高于CC基因型患者[116.7±78.2）ng.ml-1·mg-1·kg-1,P＜0.01].移植表达CYP3A5蛋白（＊1基因型）供体的患者中,不同供体IL-18基因型患者C/D值（ng.ml-1·mg-1·kg-1） （GG＋ GC：133.4±65.3;CC：88.3±39.9）差异有统计学意义（P＜0.05）.结论 联合检测供体CYP3A5rs776746和IL-18 rs5744247基因型有助于指导他克莫司个体化用药.Objective To investigate the effect of cytochrome P450 3A family polypeptide 5 （CYP3A5） and interleukin-18 （IL-18） polymorphisms on the concentration/dose ratio of tacrolimus in Chinese liver transplant patients.Methods Donor CYP3A5 polymorphisms at rs776746 and IL-18 polymorphisms at rs5744247 were assessed by polymerase chain reaction （PCR） amplification and DNA sequencing for 84 liver transplant patients.The relationship between gene polymorphism and tacrolimus concentration/dose ralio was analyzed.Results The tacrolimus C/D ratios（ng.ml-1 ·mg-1 · kg-1） of the recipients with donors who were IL-18 rs5744247 GG ＋ GC （163.1 ± 100.8） genotype were higher than those with donors who were CC genotype （116.7 ± 78.2,P ＜ 0.001）.The tacrolimus C/D ratios of the recipients with donors who were CYP3A5 expressors and had IL-18 rs5744247 GG ＋ GC genotype （133.4 ± 65.3） were higher than those with donors who were CYP3A5 expressors and had IL-18 rs5744247 CC genotype （88.3 ± 39.9,P ＜ 0.05）.Conclusion Determination of donor CYP3A5 and IL-18 genotype may be performed prospectively to help individualizing tacrolimus dose regimen for liver transplant patients.

关 键 词：肝移植 他克莫司 细胞色素P4503A亚家族多肽5 白细胞介素-18 基因多态性 

分 类 号：R657.3[医药卫生—外科学]