The impact of liver transplant recipient and donor genetic variability on tacrolimus exposure and transplant outcome

Abstract

This study investigated the effect of recipient and donor genetic variability on dose‐adjusted steady‐state tacrolimus concentrations (C _ss) and clinical outcomes 3 and 6 months after liver transplant. Twenty‐nine recipients and matched donor blood samples were genotyped for 27 single nucleotide polymorphisms including CYP3A5*3 (rs776746), ABCB1 haplotype and immune genes. Associations between genetic variability and clinical parameters and C _ss and the occurrence of rejection and nephrotoxicity were analysed by multivariate and multinomial logistic regression modelling and Jonckheere–Terpstra tests examined the impact of combined donor/recipient CYP3A5 expression on C _ss. At 3 months post‐transplant modelling revealed an association between tacrolimus C _ss and recipient CASP1 rs580523 genotype ( P = 0.005), accounting for 52% C _ss variance. Jonckheere–Terpstra tests revealed that as combined donor/recipient CYP3A5 expression increased, C _ss decreased ( P = 0.010 [3 months], 0.018 [6 months]). As this is the first report of CASP1 genetic variability influencing tacrolimus C _ss, further validation in larger cohorts is required.