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


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.

SUBMITTER: Oetting WS 

PROVIDER: S-EPMC6597284 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Oetting William S WS   Wu Baolin B   Schladt David P DP   Guan Weihua W   van Setten Jessica J   Keating Brendan J BJ   Iklé David D   Remmel Rory P RP   Dorr Casey R CR   Mannon Roslyn B RB   Matas Arthur J AJ   Israni Ajay K AK   Jacobson Pamala A PA  

Transplantation 20190601 6


<h4>Background</h4>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.<h4>Methods</h4>We performed a genome-wide association study, using a genotyping array tailored specifically for transpl  ...[more]

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