Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients. (February 2018)

• Record Type: Journal Article
• Authors: Oetting, William S; Wu, Baolin; Schladt, David P; Guan, Weihua; Remmel, Rory P; Dorr, Casey; Mannon, Roslyn B; Matas, Arthur J; Israni, Ajay K; Jacobson, Pamala A
• Is Part Of: Pharmacogenomics. Volume 19:Number 3(2018)
• Page Start: 175
• Page End: 184
• Publication Date: 2018-02
• Subjects: CYP3A5 -- GWAS -- kidney -- tacrolimus -- transplantation; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2017-0187
• Languages: English
• ISSNs: 1462-2416

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.