CYP3A5和补体C5的基因多态性对肝移植术后早期血他克莫司浓度的影响  

Association of CYP3A5 and C5 polymorphisms with the individual dosage regimen of tacrolimus in Chinese liver transplantation recipients during the early post-transplantation period

作　　者：廖建华[1] 李常灿 王兆文[1] 樊军卫[1] 彭志海[1] Liao Jianhua Li Changchan Wang Zhaowen Fan Junwei Peng Zhihai

机构地区：[1]上海交通大学附属第一人民医院普外科,200080

出　　处：《中华器官移植杂志》2017年第5期292-296,共5页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金资助项目（81370579）;上海市科学技术委员会基金资助项目（134119a6300）;上海交通大学“科技创新专项基金”资助项目（YG2012MS05）

摘　　要：目的 探讨肝移植供、受者细胞色素P4503A亚家族多肽5（CYP3 A5）和补体C5（C5）基因多态性对受者术后早期血他克莫司浓度的影响.方法 应用测序技术检测100对肝移植供、受者CYP3A5 rs776746和C5 rs17611位点的单核苷酸多态性,观察受者术后1周内的全血他克莫司浓度谷值（C0）和给药剂量,计算C0与剂量比值（C0/D值）,分析基因多态性与他克莫司代谢的相关性.结果 供、受者C5 rs17611位点主要等位基因均为A,占比分别为63.5％和58.5％;CYP3A5rs776746位点主要等位基因均为G,占比分别为71％和72％.肝移植术后3d后,C5rs17611基因型为AA受者的C0/D值显著低于携带等位基因G的受者（P＜0.05）,肿瘤组受者C0/D值明显高于非肿瘤组（P＜0.05）,而供者C5rs17611基因型与受者C0/D值未发现明显统计学相关性（P＞0.05）.供、受者CYP3A5rs776746位点基因多态性与受者的C0/D值均明显相关（P＜0.05）.C5rs17611与CYP3A5 rs776746位点不存在连锁不平衡关系（D＇max=0.392,r2max=0.034）.两位点联合分析发现,随着受者携带快代谢基因的个数增加,术后1周内受者体内他克莫司代谢速度也随之增加,C0/D值明显下降（P=0.012,P＜0.001,P＜0.001和P=0.002）.结论 联合检测供、受者CYP3A5rs776746和C5rs17611基因型有助于指导肝移植受者术后早期他克莫司的个体化用药.Objective To investigate the effect of CYP3A5 and C5 gene polymorphisms on the concentration/dose ratio of tacrolimus in Chinese liver transplant patients during the early posttransplantation period.Methods A total of 100 adult patients who underwent primary liver transplantation （LT） were enrolled.Tacrolimus dosage and trough blood concentration were detemined at first week after liver transplantation.Two single-nucleotide polymorphisms were genotyped and analyzed in both donor and recipient groups.The relationship between gene polymorphisms and tacrolimus concentration/dose ratio （C/ D ratio） was analyzed.Results The distribution of allele A in C5 rs17611 was 63.5 % among donors and 58.5% among recipients.For CYP3A5,the rs776746 allele G represented the major alleles in both donors and recipients （71% and 72%,respectively）.The tacrolimus C/D ratio of recipients carrying allele AA in C5 rs17611 was significantly higher than that of recipients carrying the C5 rs17611 allele G.Both donor and recipient CYP3A5 rs776746 polymorphisms were highly correlated with the tacrolimus C/D ratio at first week after liver transplantation.No linkage disequilibrium between CYP3A5 rs776746 and C5 rs17611 polymorphisms was found （D＇max =0.392,r2max =0.034）.Recipient CYP3A5 rs776746 allele A,C5 rs17611 genotype AA,and donor CYP3A5 rs776746 allele A were associated with rapid tacrolimus metabolism.With increasing number of these alldes,tacrolimus C/D ratio was reduced during the one week after transplantation.Conclusion Recipient C5 rs17611 polymorphism is a new genetic locus that influences tacrolimus metabolism in patients after OLT during the early post-transplantation periocd.

关 键 词：肝移植 他克莫司 细胞色素P4503A亚家族多肽5 补体C5 基因多态性 

分 类 号：R657.3[医药卫生—外科学]