Department of Pharmacology and Toxicology, CHU Limoges, Limoges, France.
INSERM, UMR 1248, Limoges, France.
Am J Transplant. 2018 Dec;18(12):2905-2913. doi: 10.1111/ajt.14894. Epub 2018 Jun 1.
This work investigated, in two large cohorts of French renal transplants treated with tacrolimus, the influence of donor and recipient ABCB1, CYP3A4, and CYP3A5 genotypes on the risk of allograft loss. A discovery and a replication population of 330 and 369 adult renal transplant patients, each from a different transplantation center and all receiving a tacrolimus-based immunosuppressive regimen, were retrospectively genotyped. The influence of genetic factors and other known risk factors on allograft loss was investigated using multivariate Cox proportional hazard analyses. The existence of previous transplantations (per unit HR = 1.89 [1.10-3.26] P = .0216) and the donor ABCB1 c.1199GA/AA genotype (GA/AAvs GG: HR = 3.22 [1.14-9.09], P = .0288) were associated with an increased risk of allograft loss in the discovery cohort and with graft loss due to humoral rejection in the replication cohort (per unit HR = 2.26 [1.34-3.81], P = .00229; GA/AAvs GG HR = 3.42 [1.28-9.16], P = .0142). Genotyping the donor for the ABCB1 c.1199 G>A (exon 11, rs2229109) allele may be of interest before prescribing tacrolimus to the recipient, although this polymorphism is rather rare and its effect may be limited to certain mechanisms of graft loss.
本研究在两个大型法国肾移植队列中探讨了供体和受者 ABCB1、CYP3A4 和 CYP3A5 基因型对同种异体移植物丢失风险的影响。对来自不同移植中心、均接受他克莫司为基础的免疫抑制方案治疗的 330 名和 369 名成年肾移植患者的发现和复制人群进行了回顾性基因分型。使用多变量 Cox 比例风险分析研究了遗传因素和其他已知风险因素对同种异体移植物丢失的影响。先前的移植（每单位 HR=1.89[1.10-3.26]P=0.0216）和供体 ABCB1 c.1199GA/AA 基因型（GA/AAvs GG：HR=3.22[1.14-9.09]P=0.0288）与发现队列中同种异体移植物丢失风险增加以及复制队列中移植物丢失与体液排斥有关（每单位 HR=2.26[1.34-3.81]P=0.00229；GA/AAvs GG HR=3.42[1.28-9.16]P=0.0142）。在为受者开他克莫司之前，对供体的 ABCB1 c.1199G>A（外显子 11，rs2229109）等位基因进行基因分型可能是有益的，尽管这种多态性相当罕见，其作用可能仅限于某些移植物丢失机制。
