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Effect of genetic polymorphisms of CYP3A5 and MDR1 on cyclosporine concentration during the early stage after renal transplantation in Chinese patients co-treated with diltiazem

  • Pharmacogenetics
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Abstract

Objective

The aim of this study was to assess the influence of the cytochrome (CYP450)3A5 and multidrug resistance (MDR1) gene polymorphisms on cyclosporine A (CsA) trough concentration during the early stage after renal transplantation in Chinese patients co-treated with diltiazem.

Methods

CYP3A5*3 (A6986G) and MDR1 C1236T, G2677T/A and C3435T polymorphisms were determined by PCR followed by restriction fragment length polymorphism (RFLP) analysis. A total of 112 Chinese renal transplant patients were enrolled in the study. The whole blood trough concentration was measured at 7 days after transplantation, and the dose-adjusted trough levels were compared among the different genotypes.

Results

The dose-adjusted trough levels of CsA were significantly higher in MDR1 2677TT carriers than in GG plus GT carriers (59.5 ± 15.9 vs. 34.5 ± 9.4 vs. 43.2 ± 13.6 ng/mL per mg per kg; P < 0.0001). In patients who were co-treated with diltiazem, compared with carriers of haplotype T-T-C, the carriers of haplotype C-G-C and haplotype T-G-T had significantly lower dose-adjusted trough blood concentrations of CsA than the non-carrier group (P = 0.002, P = 0.000 and P = 0.000, respectively). However, no evidence was found that there was a relationship between the CYP3A5*3, MDR1 C1236T and MDR1 C3435T polymorphisms and CsA dose-adjusted trough concentrations.

Conclusion

This study demonstrated that the G2677T/A single nucleotide polymorphisms in MDR1 and MDR1 haplotypes C-G-C, T-G-T and T-T-C are associated with the CsA concentration during the very early post-transplant period in Chinese renal transplant patients co-treated with diltiazem. These polymorphisms may be useful for determining the appropriate initial dose of CsA after renal transplantation.

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Acknowledgements

This work was supported by the National Nature Science Fund of China (No. 30572231). We thank all doctors, nurses and patients who took part in this study. This study was supported by the Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, the First Affiliated Hospital of Sun Yat-sen University. The Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University approved the study. The authors declare that there are no competing interests.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong Province, China

    Yixi Wang, Jiali Li, Xueding Wang, Huichang Bi & Min Huang

  2. Department of Organ Transplant, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China

    Changxi Wang & Genglong Zhu

  3. Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China

    Xiao Chen

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  1. Yixi Wang
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Correspondence to Min Huang.

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Wang, Y., Wang, C., Li, J. et al. Effect of genetic polymorphisms of CYP3A5 and MDR1 on cyclosporine concentration during the early stage after renal transplantation in Chinese patients co-treated with diltiazem. Eur J Clin Pharmacol 65, 239–247 (2009). https://doi.org/10.1007/s00228-008-0577-4

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