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Observational Study
. 2019 Jun;103(6):1131-1139.
doi: 10.1097/TP.0000000000002625.

Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies

William S Oetting  1 , Baolin Wu  2 , David P Schladt  3 , Weihua Guan  2 , Jessica van Setten  4 , Brendan J Keating  5 , David Iklé  6 , Rory P Remmel  7 , Casey R Dorr  3   8 , Roslyn B Mannon  9 , Arthur J Matas  10 , Ajay K Israni  3   11   12 , Pamala A Jacobson  1 ; DeKAF Genomics and GEN-03 Investigators
Affiliations
Observational Study

Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies

William S Oetting et al. Transplantation. 2019 Jun.

Abstract

Background: The immunosuppressants tacrolimus and mycophenolate are important components to the success of organ transplantation, but are also associated with adverse effects, such as nephrotoxicity, anemia, leukopenia, and new-onset diabetes after transplantation. In this report, we attempted to identify genetic variants which are associated with these adverse outcomes.

Methods: We performed a genome-wide association study, using a genotyping array tailored specifically for transplantation outcomes containing 722 147 single nucleotide polymorphisms, and 2 cohorts of kidney allograft recipients-a discovery cohort and a confirmation cohort-to identify and then confirm genetic variants associated with immunosuppressant pharmacokinetics and adverse outcomes.

Results: Several genetic variants were found to be associated with tacrolimus trough concentrations. We did not confirm variants associated with the other phenotypes tested although several suggestive variants were identified.

Conclusions: These results show that adverse effects associated with tacrolimus and mycophenolate are complex, and recipient risk is not determined by a few genetic variants with large effects with but most likely are due to many variants, each with small effect sizes, and clinical factors.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

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