A donor and recipient candidate gene association study of allograft loss in renal transplant recipients receiving a tacrolimus‐based regimen

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. This study in two large cohorts of renal transplant patients treated with tacrolimus shows an association between the donor genotype for a single‐nucleotide polymorphism in the efflux transporter P‐glycoprotein and an increased risk of allograft loss in the discovery cohort and with graft loss due to humoral rejection in the replication cohort.