Abstract
Tacrolimus is a widely used immunosuppressive drug for preventing the rejection of solid organ transplants. The efficacy of tacrolimus shows considerable variability, which might be related to genetic variation among recipients. We conducted a retrospective study of 240 Chinese renal transplant recipients receiving tacrolimus as immunosuppressive drug. The retrospective data of all patients were collected for 40 days after transplantation. Seventeen SNPs of CYP3A5, CYP3A4, COMT, IL-10 and POR were identified by the SNaPshot assay. Tacrolimus blood concentrations were obtained on days 1–3, days 6–8 and days 12–14 after transplantation, as well as during the period of the predefined therapeutic concentration range. Kruskal–Wallis test was used to examine the effect of genetic variation on the tacrolimus concentration/dose ratio (C 0/D) at different time points. Chi-square test was used to compare the proportions of patients who achieved the target C 0 range in the different genotypic groups at weeks 1, 2, 3 and 4 after transplantation. After correction for multiple testing, there was a significant association of C 0/D with CYP3A5*3, CYP3A4*1G and CYP3A4 rs4646437 T>C at different time points after transplantation. The proportion of patients in the IL-10 rs1800871-TT group who achieved the target C 0 range was greater (p = 0.004) compared to the IL-10 rs1800871-CT and IL-10 rs1800871-CC groups at week 3 after transplantation. CYP3A5*3, CYP3A4 *1G, CYP3A4 rs4646437 T>C and IL-10 rs1800871 C>T might be potential polymorphisms affecting the interindividual variability in tacrolimus metabolism among Chinese renal transplant recipients.
Highlights
Tacrolimus is an effective immunosuppressive drug widely used in solid organ transplantation to prevent rejection [1]
The same results were found between patients with the CYP3A4 rs4646437 T allele and the CYP3A4 rs4646437 CC genotype. This retrospective study examined the contribution of gene polymorphisms to the dose-adjusted tacrolimus concentration (C0/ D) and the length of time required to reach the target trough blood concentration range (C0) in Chinese renal transplant recipients
This result further validated that the CYP3A5*3 allele was strongly associated with tacrolimus pharmacokinetics
Summary
Tacrolimus is an effective immunosuppressive drug widely used in solid organ transplantation to prevent rejection [1]. It is characterized by a narrow therapeutic range and large inter- and intraindividual variability in its pharmacokinetics [2]. Dose requirement and the length of time required to reach the target C0 range show significant interindividual and interethnic variability. Full understanding of this mechanism is highly desirable for the patients to improve the therapeutic efficacy and reduce the side effects
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