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. 2017 Jun 13;7(1):3429.
doi: 10.1038/s41598-017-02698-w.

The correlation between the expression of genes involved in drug metabolism and the blood level of tacrolimus in liver transplant receipts

Jianhai Wang  1 , Keqiu Li  1 , Xiaoning Zhang  1 , Dahong Teng  2 , Mingyan Ju  1 , Yaqing Jing  1 , Yuxia Zhao  1 , Guang Li  3
Affiliations

The correlation between the expression of genes involved in drug metabolism and the blood level of tacrolimus in liver transplant receipts

Jianhai Wang et al. Sci Rep. .

Abstract

Immunosuppressive medications, such as tacrolimus and mycophenolate mofetil, are commonly used for reducing the risk of organ rejection in receipts of allogeneic organ transplant. The optimal dosages of these drugs are required for preventing rejection and avoiding toxicity to receipts. This study aimed to identify the correlation between the expression profiling of genes involved in drug metabolism and the blood level of tacrolimus in liver transplant receipts. Sixty-four liver transplant receipts were enrolled in this retrospective study. Receipts were divided into low (2-5.9 ng/ml) and high (6-15 ng/ml) tacrolimus groups. Clinical assessment showed that the blood level of tacrolimus was inversely correlated with the liver function evaluated by blood levels of total bilirubin and creatinine. Compared to the high tacrolimus group, expression levels of six cytochrome P450 enzymes, CYP1A1, CYP2B6, CYP3A5, CYP4A11, CYP19A1, and CYP17A1 were significantly higher in the low tacrolimus group. The expression levels of these genes were negatively correlated with the tacrolimus blood level. Enzyme assays showed that CYP3A5 and CYP17A1 exerted direct metabolic effects on tacrolimus and mycophenolate mofetil, respectively. These results support clinical application of this expression profiling of genes in drug metabolism for selection of immunosuppressive medications and optimal dosages for organ transplant receipts.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
The correlation between the blood tacrolimus level and the blood levels of total bilirubin and creatinine in liver transplant receipts.
Figure 2
Figure 2
Heat map of three human drug metabolism PCR arrays. (A) Drug metabolism PCR array, (B) Phase I enzymes PCR array, (C) Phase II enzymes PCR array. Gene expression levels in low and the high tacrolimus (Tac) groups in liver transplant receipts are shown.
Figure 3
Figure 3
Validation of gene expression levels in the blood of low and the high tacrolimus (Tac) groups in liver transplant receipts. RNA from the blood of receipts was prepared for real-time PCR analysis of gene expression levels. Relative expression levels of indicated genes are shown. The average of the gene expression level from the low Tac group was set as 1, and gene expression levels in receipts were compared to this value.
Figure 4
Figure 4
Linear regression analysis of the correlation between the blood tacrolimus level and the indicated gene expression level in liver transplant receipts.
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References

    1. Bernal, W. et al. (2015) Acute-on-ch ronic liver failure. Lancet386, 1576–1587 (2015). - PubMed
    1. Choi, S. W. & Reddy, P. Current and emerging strategies for the prevention ofgraft-versus-host disease. Nat. Rev. Clin. Oncol. 11, 536–547, doi:10.1038/nrclinonc.2014.102 (2014). - PMC - PubMed
    1. Adams DH, Sanchez-Fueyo A, Samuel D. From immunosuppression to tolerance. J. Hepato. 2015;62:S170–85. doi: 10.1016/j.jhep.2015.02.042. - DOI - PubMed
    1. Dai Y, et al. Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro. Drug metabolism and disposition: the biological fate of chemicals. Drug Metab. Dispos. 2006;34:836–47. doi: 10.1124/dmd.105.008680. - DOI - PubMed
    1. Saeki T, et al. Human P-glycoprotein transports cyclosporin A and FK506. J. Biol. Chem. 1993;268:6077–80. - PubMed

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