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FKBP1A rs6041749 polymorphism is associated with allograft function in renal transplant patients

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aim

To investigate the potential impact of single-nucleotide polymorphisms (SNPs) in the FK506-binding protein (FKBP)-calcineurin (CaN)-nuclear factor of activated T cells (NFAT) signaling pathway on the efficacy and safety of tacrolimus (TAC) in Chinese renal transplant patients.

Methods

Seventy-seven tag SNPs were detected in 146 patients who were on TAC-based maintenance immunosuppression and who followed up for at least 2 years. The relationships of these polymorphisms with clinical outcomes such as acute rejection, acute nephrotoxicity, pneumonia, and estimated glomerular filtration rate (eGFR) were explored. For the FKBP1A rs6041749 polymorphism, which has a significant association with renal function over time, a preliminary functional analysis was performed using a dual-luciferase reporter gene system.

Results

The patients with FKBP1A rs6041749 TT genotype had a more stable eGFR level than CC and CT carriers (P = 2.08 × 10−8) during the 2 years following transplantation. Dual-luciferase reporter assay results showed that the rs6041749 C variant could enhance the relative luciferase activity compared with the T variant, which indicated that the rs6041749 C allele may increase the FKBP1A gene transcription. In addition, we did not find any association between these genetic variants and the risk of acute rejection, acute nephrotoxicity, and pneumonia in renal transplant patients receiving TAC-based immunosuppression.

Conclusions

FKBP1A rs6041749 C allele carriers are at higher risk for eGFR deterioration. The variant might serve as a biomarker to predict allograft function in renal transplant patients.

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Contribution of the authors

XYQ conceived the study. XYQ, ZJ, and MKZ participated in research design. XYQ, QXX, LYX, ZJ, and MZ contributed to acquisition of the patients’ data. ZW performed the research and analyzed the data. ZW and XYQ drafted and all the authors revised the manuscript.

Funding

Dr. Xiaoyan Qiu had support from the National Natural Science Foundation of China (No. 81302854) and Natural Science Foundation of Shanghai (No. 13ZR1405200).

Prof. Zheng Jiao was supported by the National Natural Science Foundation of China (No. 81573505) and the Guidance Project of Shanghai Municipal Science and Technology Commission (15411968000) and “Weak Discipline Construction Project” (No. 2016ZB0301–01) of Shanghai Municipal Commission of Health and Family Planning.

Prof. Mingkang Zhong was supported by “2016 Key Clinical Program of Clinical Pharmacy.”

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Authors and Affiliations

  1. Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, China

    Zhuo Wu, Qinxia Xu, Xiaoyan Qiu, Luyang Xu, Zheng Jiao & Mingkang Zhong

  2. Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China

    Ming Zhang

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  1. Zhuo Wu
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Correspondence to Xiaoyan Qiu.

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The study was performed in accordance with the Declaration of Helsinki and its amendments. Protocols were approved by the Ethics Committee of Huashan Hospital, Fudan University and written informed consents were obtained from all subjects.

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The authors declare that they have no competing interests.

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Wu, Z., Xu, Q., Qiu, X. et al. FKBP1A rs6041749 polymorphism is associated with allograft function in renal transplant patients. Eur J Clin Pharmacol 75, 33–40 (2019). https://doi.org/10.1007/s00228-018-2546-x

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  • DOI: https://doi.org/10.1007/s00228-018-2546-x

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