2011
DOI: 10.1097/tp.0b013e318200e991
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Novel Polymorphisms Associated With Tacrolimus Trough Concentrations: Results From a Multicenter Kidney Transplant Consortium

Abstract: Background The CYP4503A5*1 genotype is associated with lower tacrolimus concentrations. Although its effect is important, it incompletely explains the variability in tacrolimus concentrations and has a relatively low minor allele frequency in Caucasians relative to African Americans (AA). Methods We studied clinical and recipient genetic correlates of dose-normalized tacrolimus troughs (n=12,277) in the first 6 months posttransplant using a customized single nucleotide polymorphism chip with 2,722 variants i… Show more

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Cited by 159 publications
(142 citation statements)
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“…It is well documented that, largely because of a high frequency of the CYP3A5 genetic polymorphism (which acts to increase the clearance and lower the oral bioavailability of tacrolimus), blacks require higher tacrolimus drug doses to achieve the same drug level achieved by nonblacks. [20][21][22][23][24][25][26] Specifically, the wild-type gene CYP3A5*1, which allows significant production of cytochrome P450 3A5, is reportedly absent in 60% to 90% of nonblacks and yet is present in 55% of blacks. This may partially account for lower tacrolimus troughs and higher tacrolimus dose requirements among blacks.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…It is well documented that, largely because of a high frequency of the CYP3A5 genetic polymorphism (which acts to increase the clearance and lower the oral bioavailability of tacrolimus), blacks require higher tacrolimus drug doses to achieve the same drug level achieved by nonblacks. [20][21][22][23][24][25][26] Specifically, the wild-type gene CYP3A5*1, which allows significant production of cytochrome P450 3A5, is reportedly absent in 60% to 90% of nonblacks and yet is present in 55% of blacks. This may partially account for lower tacrolimus troughs and higher tacrolimus dose requirements among blacks.…”
Section: Discussionmentioning
confidence: 99%
“…in week 26; blood samples were taken before dosing and 0.5, 1, 1.5, 2, 3, 4,6,8,12,16,20, and 24 hours after dosing.…”
Section: Study Design and Conductmentioning
confidence: 99%
“…Additional variants were genotyped using the SNPlex (Applied Biosystems, Foster City, CA, USA) and Sequenom (Sequenom, San Diego, CA, USA) systems. In a prior analysis, these variants were evaluated for their association with dose-normalized tacrolimus concentrations using standard regression analysis [20].As it was not feasible to evaluate 2724 variants and their combinations in a population pharmacokinetic approach to estimate CL/F, the SNPs with a P value < 0.01 from the AA and non-AA populations from the regression analysis, were selected for this analysis. The variants evaluated towards tacrolimus were rs776746, rs12114000, rs3734354, rs4926, rs3135506 and rs2608555.…”
Section: Genotyping and Selection Of Variants For Analysismentioning
confidence: 99%
“…Результаты многоцентровых исследований [8], в которых были использованы стандартные дозы такролимуса, показали его трансформацию в орга-низме в зависимости от генотипа CYP3A5 (рис. 3).…”
Section: èíòåðïðåòàöèÿ ôàðìàêîãåíîòèïèðîâàíèÿ Cyp3a5unclassified