Attempted Validation of 44 Reported SNPs Associated with Tacrolimus Troughs in a Cohort of Kidney Allograft Recipients

Abstract

Aim: Multiple genetic variants have been associated with variation in tacrolimus (TAC) trough concentrations. Unfortunately, additional studies do not confirm these associations, leading one to question if a reported association is accurate and reliable. We attempted to validate 44 published variants associated with TAC trough concentrations. Materials & methods: Genotypes of the variants in our cohort of 1923 kidney allograft recipients were associated with TAC trough concentrations. Results: Only variants in CYP3A4 and CYP3A5 were significantly associated with variation in TAC trough concentrations in our validation. Conclusion: There is no evidence that common variants outside the CYP3A4 and CYP3A5 loci are associated with variation in TAC trough concentrations. In the future rare variants may be important and identified using DNA sequencing.

Keywords::

• CYP3A5
• GWAS
• kidney
• tacrolimus
• transplantation

Acknowledgements

The authors wish to thank the research subjects for their participation in this study. We acknowledge the dedication and hard work of our coordinators at each of the DeKAF Genomics clinical sites: University of Alberta, N Bobocea, T Wong, A Geambasu and A Sader; University of Manitoba, M Ross and K Peters; University of Minnesota, M DeGrote, M Myers and D Berglund; Hennepin County Medical Center, L Berndt; Mayo Clinic, T DeLeeuw; University of Iowa, W Wallace and T Lowe; University of Alabama, J Vaughn, V Stephens and T Hilario. We also acknowledge the dedicated work of our research scientists M Brott and A Muthusamy.

Financial & competing interests disclosure

This study was supported in part by NIH/NIAID grants 5U19-AI070119 and 5U01-AI058013. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported in part by NIH/NIAID grants 5U19-AI070119 and 5U01-AI058013. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript