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Pharmacogenotyping of CYP3A5 in predicting dose-adjusted trough levels of tacrolimus among Malaysian kidney-transplant patients


Hamzah, Sharina and Teh, Lay Kek and Shia, John Kwong Siew and Ahmad, Ghazali and Wong, Hin Seng and Zakaria, Zainul Amiruddin and Salleh, Mohd Zaki (2014) Pharmacogenotyping of CYP3A5 in predicting dose-adjusted trough levels of tacrolimus among Malaysian kidney-transplant patients. Canadian Journal of Physiology and Pharmacology , 92 (1). pp. 50-57. ISSN 0008-4212; ESSN: 1205-7541


Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05-3.70 (ng·mL(-1))/(mg·kg(-1))) as compared with the expressors (1.15, 95%: 0.95-1.80 (ng·mL(-1))/(mg·kg(-1))) of CYP3A5 (Mann-Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA level with L/D was demonstrated (Spearman's Rank Order correlation; P = 0.016, rs = -0.348). However, in multiple regression analysis, only CYP3A5*3 genotype groups were found to be significantly correlated with tacrolimus L/D (P < 0.001). These findings highlight the importance of CYP3A5*3 pharmacogenotyping among kidney-transplant patients treated with tacrolimus, and confirm the role of blood cell P-glycoprotein in influencing the L/D for tacrolimus.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Medicine and Health Science
DOI Number: https://doi.org/10.1139/cjpp-2013-0128
Publisher: NRC Research Press
Keywords: Kidney transpant patients; Tacrolimus; CYP3A5 genotype; ABCB1 genotype; mRNA copy number of ABCB1
Depositing User: Nurul Ainie Mokhtar
Date Deposited: 23 Dec 2015 08:03
Last Modified: 23 Dec 2015 08:03
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1139/cjpp-2013-0128
URI: http://psasir.upm.edu.my/id/eprint/34894
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