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
Department of Experimental & Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA.
Pharmacogenomics. 2018 Feb;19(3):175-184. doi: 10.2217/pgs-2017-0187. Epub 2018 Jan 10.
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.
Only variants in CYP3A4 and CYP3A5 were significantly associated with variation in TAC trough concentrations in our validation.
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.
多种基因变异与他克莫司（TAC）谷浓度的变化有关。遗憾的是，后续研究并未证实这些关联，这让人质疑所报道的关联是否准确可靠。我们试图验证44个已发表的与TAC谷浓度相关的变异。
在我们1923例肾移植受者队列中，这些变异的基因型与TAC谷浓度相关。
在我们的验证中，只有CYP3A4和CYP3A5中的变异与TAC谷浓度的变化显著相关。
没有证据表明CYP3A4和CYP3A5基因座以外的常见变异与TAC谷浓度的变化有关。未来，罕见变异可能很重要，可通过DNA测序进行识别。
