INTRODUCTION: Chronic kidney disease (CKD) after liver transplantation (LT) is a major clinical problem that appears to be associated with nongenetic as well as genetic determinants. Calcineurin inhibitor (CNI) use is considered to play a major role in the development of CKD after LT. We studied the influence of single-nucleotide polymorphisms (SNPs) in the genes of the donor and recipient CNI-metabolizing enzyme CYP3A5 and the CNI-transporting ABCB1 on the development of CKD after LT. MATERIALS AND METHODS: Tacrolimus (Tac) predose concentrations at different time-points after transplantation and the CYP3A5 6986A>G and ABCB1 3435C>T SNPs were determined in 125 LT recipients and their respective donors to study the influence of Tac predose levels and genetics on the development of CKD. RESULTS: After a median follow-up of 5.7±2.9 years, CKD developed in 47 patients (36%). The Tac predose levels were not correlated with the development of CKD. Neither did we find a correlation between the investigated SNPs in either donor or recipient ABCB1 and CYP3A5 genes (or combinations thereof) and the development of CKD. These genetic variations did not relate to Tac predose blood concentrations in our study. CONCLUSION: An individual's risk of developing CKD after LT is not associated with genetic variation in either recipient or donor CYP3A5 or ABCB1 genotype status. Copyright

ABCB1, chronic kidney disease, cytochrome P450, liver transplantation, pharmacogenetics, tacrolimus
dx.doi.org/10.1097/FPC.0000000000000063, hdl.handle.net/1765/82647
Pharmacogenetics and Genomics
Department of Internal Medicine

Tapirdamaz, Ö, Hesselink, D.A, El Bouazzaoui, S, Azimpour, M, Hansen, B.E, van der Laan, L.J.W, … Metselaar, H.J. (2014). Genetic variance in ABCB1 and CYP3A5 does not contribute toward the development of chronic kidney disease after liver transplantation. Pharmacogenetics and Genomics, 24(9), 427–435. doi:10.1097/FPC.0000000000000063