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FOXP3 rs3761548 polymorphism is associated with tacrolimus-induced acute nephrotoxicity in renal transplant patients

Zhuo Wu1, Qinxia Xu1, Xiaoyan Qiu2

  • 1Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China.

European Journal of Clinical Pharmacology
|October 18, 2016
PubMed
Abstract

Insights

The FOXP3 rs3761548 gene variant significantly increases the risk of tacrolimus (TAC)-induced nephrotoxicity in renal transplant patients. This finding may help personalize TAC therapy and prevent kidney damage.

Area of Science:

  • Nephrology
  • Pharmacogenomics
  • Immunosuppression

Background:

  • Tacrolimus (TAC) is a vital immunosuppressant post-renal transplantation.
  • Individual responses to TAC vary, necessitating personalized treatment strategies.
  • Genetic factors may influence TAC efficacy and toxicity.

Purpose of the Study:

  • To investigate the impact of FOXP3 and CCDC22 gene polymorphisms on TAC efficacy and safety in Chinese renal transplant recipients.
  • To identify genetic markers associated with TAC-induced nephrotoxicity and acute rejection.

Main Methods:

  • Genotyping of FOXP3 (rs3761547, rs3761548, rs3761549, rs2232365, rs2280883) and CCDC22 (rs2294021) polymorphisms in 114 renal transplant patients on TAC.
  • Kaplan-Meier and Cox regression analyses for clinical outcomes (acute rejection, nephrotoxicity, pneumonia).
  • Linear mixed models assessed the impact on estimated glomerular filtration rate (eGFR) over time.

Main Results:

  • Patients with FOXP3 rs3761548 AA and AC genotypes exhibited a 10-fold higher risk of TAC-induced acute nephrotoxicity compared to the CC genotype.
  • No significant associations were found between other investigated genetic variants and TAC-related outcomes.

Conclusions:

  • FOXP3 rs3761548 polymorphism is associated with TAC-induced acute nephrotoxicity in renal transplant patients.
  • This polymorphism may serve as a predictive biomarker for TAC toxicity.
  • Findings support the development of individualized TAC therapy to mitigate adverse effects.
Keywords:
FOXP3NephrotoxicityPolymorphismsRenal transplantTacrolimus

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