William S Oetting1, Baolin Wu2, David P Schladt3, Weihua Guan2, Rory P Remmel4, Casey Dorr3,5, Roslyn B Mannon6, Arthur J Matas7, Ajay K Israni3,8,9, Pamala A Jacobson1. 1. Department of Experimental & Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA. 2. Department of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA. 3. Minneapolis Medical Research Foundation, Minneapolis, MN 55404, USA. 4. Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. 5. Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA. 6. Division of Nephrology, University of Alabama, Birmingham, AL 35233, USA. 7. Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA. 8. Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA. 9. Department of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
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.
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.
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