Title |
Pharmacogenotyping of CYP3A5 in predicting dose-adjusted trough levels of tacrolimus among Malaysian kidney-transplant patients
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Published in |
Canadian Journal of Physiology and Pharmacology, December 2013
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DOI | 10.1139/cjpp-2013-0128 |
Pubmed ID | |
Authors |
Sharina Hamzah, Lay Kek Teh, John Shia Kwong Siew, Ghazali Ahmad, Hin Seng Wong, Zainul Amiruddin Zakaria, Mohd Zaki Salleh |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 18 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 3 | 17% |
Student > Doctoral Student | 2 | 11% |
Student > Master | 2 | 11% |
Researcher | 2 | 11% |
Student > Ph. D. Student | 2 | 11% |
Other | 4 | 22% |
Unknown | 3 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 33% |
Medicine and Dentistry | 4 | 22% |
Biochemistry, Genetics and Molecular Biology | 2 | 11% |
Unspecified | 1 | 6% |
Computer Science | 1 | 6% |
Other | 1 | 6% |
Unknown | 3 | 17% |